Genetic Variant SLC4A3:p.Ser120Ser (chr2-219629286-C-G) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_005070.4(SLC4A3):c.360C>G(p.Ser120Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S120S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC4A3
NM_005070.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -7.36

Publications

1 publications found

Variant links:

Genes affected

SLC4A3 (HGNC:11029): (solute carrier family 4 member 3) The protein encoded by this gene is a plasma membrane anion exchange protein. The encoded protein has been found in brain, heart, kidney, small intestine, and lung. [provided by RefSeq, May 2016]

SLC4A3 Gene-Disease associations (from GenCC):

short QT syndrome 7
Inheritance: AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
short QT syndrome
Inheritance: AD Classification: MODERATE Submitted by: G2P, ClinGen
autosomal dominant distal renal tubular acidosis
Inheritance: AD Classification: LIMITED Submitted by: Franklin by Genoox

SLC4A3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP7

Synonymous conserved (PhyloP=-7.36 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005070.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC4A3	NM_005070.4	MANE Select	c.360C>G	p.Ser120Ser	synonymous	Exon 4 of 23	NP_005061.3	P48751-1
SLC4A3	NM_001326559.2		c.360C>G	p.Ser120Ser	synonymous	Exon 4 of 23	NP_001313488.2	P48751-3
SLC4A3	NM_201574.3		c.360C>G	p.Ser120Ser	synonymous	Exon 4 of 23	NP_963868.3	P48751-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC4A3	ENST00000358055.8	TSL:1 MANE Select	c.360C>G	p.Ser120Ser	synonymous	Exon 4 of 23	ENSP00000350756.3	P48751-1
SLC4A3	ENST00000273063.10	TSL:1	c.360C>G	p.Ser120Ser	synonymous	Exon 4 of 23	ENSP00000273063.6	P48751-3
SLC4A3	ENST00000425141.5	TSL:1	n.360C>G		non_coding_transcript_exon	Exon 4 of 23	ENSP00000396863.1	F8WD49

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249538

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461604

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727102

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53356

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111872

Other (OTH)

AF:

0.00

AC:

AN:

60378

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.0020

(source)

DANN

Benign

0.58

PhyloP100

-7.4

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over