dbSNP rs191369944: SLC4A10:c.49-62216T>G (chr2-161708757-T-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_001354441.2(SLC4A10):c.9T>G(p.Ser3Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,532,344 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 3 hom. )

Consequence

SLC4A10
NM_001354441.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.85

Publications

1 publications found

Variant links:

Genes affected

SLC4A10 (HGNC:13811): (solute carrier family 4 member 10) This gene belongs to a small family of sodium-coupled bicarbonate transporters (NCBTs) that regulate the intracellular pH of neurons, the secretion of bicarbonate ions across the choroid plexus, and the pH of the brain extracellular fluid. The protein encoded by this gene was initially identified as a sodium-driven chloride bicarbonate exchanger (NCBE) though there is now evidence that its sodium/bicarbonate cotransport activity is independent of any chloride ion countertransport under physiological conditions. This gene is now classified as a member A10 of the SLC4 family of transmembrane solute carriers. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, May 2010]

SLC4A10 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: STRONG Submitted by: ClinGen
neurodevelopmental disorder with hypotonia and characteristic brain abnormalities
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Baylor College of Medicine Research Center, PanelApp Australia, G2P

SLC4A10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 2-161708757-T-G is Benign according to our data. Variant chr2-161708757-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3777775.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.85 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00173 (262/151580) while in subpopulation NFE AF = 0.00137 (93/67638). AF 95% confidence interval is 0.00115. There are 2 homozygotes in GnomAd4. There are 157 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354441.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC4A10	NM_001178015.2	MANE Select	c.49-62216T>G		intron	N/A	NP_001171486.1	Q6U841-1
SLC4A10	NM_001354441.2		c.9T>G	p.Ser3Ser	synonymous	Exon 2 of 28	NP_001341370.1
SLC4A10	NM_001354442.2		c.9T>G	p.Ser3Ser	synonymous	Exon 2 of 28	NP_001341371.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC4A10	ENST00000446997.6	TSL:1 MANE Select	c.49-62216T>G	intron	N/A	ENSP00000393066.1	Q6U841-1
SLC4A10	ENST00000415876.6	TSL:1	c.49-62216T>G	intron	N/A	ENSP00000395797.2	Q6U841-2
SLC4A10	ENST00000461456.5	TSL:1	n.213T>G	non_coding_transcript_exon	Exon 2 of 9

Frequencies

GnomAD3 genomes

AF:

0.00173

AC:

262

AN:

151462

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000411

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00112

Gnomad ASJ

AF:

0.00116

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.0114

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00137

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.00149

AC:

199

AN:

133462

AF XY:

0.00155

show subpopulations

Gnomad AFR exome

AF:

0.000314

Gnomad AMR exome

AF:

0.000778

Gnomad ASJ exome

AF:

0.00110

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0119

Gnomad NFE exome

AF:

0.00134

Gnomad OTH exome

AF:

0.00171

GnomAD4 exome

AF:

0.00139

AC:

1916

AN:

1380764

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

962

AN XY:

681352

show subpopulations

African (AFR)

AF:

0.000669

AC:

AN:

31410

American (AMR)

AF:

0.000898

AC:

AN:

35638

Ashkenazi Jewish (ASJ)

AF:

0.00116

AC:

AN:

25016

East Asian (EAS)

AF:

0.00

AC:

AN:

35668

South Asian (SAS)

AF:

0.00126

AC:

100

AN:

79118

European-Finnish (FIN)

AF:

0.0128

AC:

433

AN:

33854

Middle Eastern (MID)

AF:

0.0123

AC:

AN:

5670

European-Non Finnish (NFE)

AF:

0.00105

AC:

1126

AN:

1076670

Other (OTH)

AF:

0.00182

AC:

105

AN:

57720

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

178

266

355

444

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00173

AC:

262

AN:

151580

Hom.:

Cov.:

AF XY:

0.00212

AC XY:

157

AN XY:

74078

show subpopulations

African (AFR)

AF:

0.000410

AC:

AN:

41462

American (AMR)

AF:

0.00112

AC:

AN:

15136

Ashkenazi Jewish (ASJ)

AF:

0.00116

AC:

AN:

3448

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.000829

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0114

AC:

121

AN:

10606

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00137

AC:

AN:

67638

Other (OTH)

AF:

0.00190

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00161

Hom.:

Bravo

AF:

0.000824

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

1.8

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over