rs1284831377

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_001321103.2(SLC4A7):c.3716G>C(p.Ser1239Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,432,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

SLC4A7
NM_001321103.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.09

Publications

0 publications found

Variant links:

Genes affected

SLC4A7 (HGNC:11033): (solute carrier family 4 member 7) This locus encodes a sodium bicarbonate cotransporter. The encoded transmembrane protein appears to transport sodium and bicarbonate ions in a 1:1 ratio, and is thus considered an electroneutral cotransporter. The encoded protein likely plays a critical role in regulation of intracellular pH involved in visual and auditory sensory transmission. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Apr 2012]

SLC4A7 Gene-Disease associations (from GenCC):

cone-rod dystrophy
Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox

SLC4A7 links:

ENSG00000287348 (HGNC:):

ENSG00000287348 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity S4A7_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15955064).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A7	NM_001321103.2 link	c.3716G>C	p.Ser1239Thr	missense_variant	Exon 26 of 26	ENST00000454389.6	NP_001308032.1	Q9Y6M7-7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A7	ENST00000454389.6 link	c.3716G>C	p.Ser1239Thr	missense_variant	Exon 26 of 26	1	NM_001321103.2	ENSP00000390394.1		Q9Y6M7-7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000409

AC:

AN:

244578

AF XY:

0.00000753

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000909

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000161

AC:

AN:

1432594

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

713646

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32822

American (AMR)

AF:

0.00

AC:

AN:

43794

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25668

East Asian (EAS)

AF:

0.00

AC:

AN:

38826

South Asian (SAS)

AF:

0.00

AC:

AN:

83804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52768

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5676

European-Non Finnish (NFE)

AF:

0.0000211

AC:

AN:

1090102

Other (OTH)

AF:

0.00

AC:

AN:

59134

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 27, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.3581G>C (p.S1194T) alteration is located in exon 25 (coding exon 25) of the SLC4A7 gene. This alteration results from a G to C substitution at nucleotide position 3581, causing the serine (S) at amino acid position 1194 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Uncertain

0.042

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.067

.;.;T;.;.;.;.;.;.;.

Eigen

Benign

-0.047

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.80

T;D;T;T;D;D;T;T;D;T

M_CAP

Benign

0.038

MetaRNN

Benign

0.16

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.60

MutationAssessor

Benign

1.2

.;.;L;.;.;.;.;.;.;.

PhyloP100

3.1

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.70

.;N;N;N;N;N;N;N;N;N

REVEL

Uncertain

0.31

Sift

Benign

0.18

.;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.68

T;T;T;T;T;T;T;T;T;T

Polyphen

0.19, 0.57

.;.;B;P;.;.;.;.;.;B

Vest4

0.18

MutPred

0.28

.;.;Gain of glycosylation at S1198 (P = 0.0148);.;.;.;.;.;.;.;

MVP

0.17

MPC

0.36

ClinPred

0.24

GERP RS

5.8

Varity_R

0.11

gMVP

0.30

Mutation Taster

=75/25

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

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rs1284831377

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over