chr3-27383186-A-G

Variant names:

• chr3-27383186-A-G
• NM_001321103.2:c.3557T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001321103.2(SLC4A7):​c.3557T>C​(p.Leu1186Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC4A7 NM_001321103.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.79
• Publications: 0 publications found

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

ENSG00000287348 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A7	NM_001321103.2	c.3557T>C	p.Leu1186Pro	missense_variant	Exon 24 of 26	ENST00000454389.6	NP_001308032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A7	ENST00000454389.6	c.3557T>C	p.Leu1186Pro	missense_variant	Exon 24 of 26	1	NM_001321103.2	ENSP00000390394.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 18, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3530T>C (p.L1177P) alteration is located in exon 24 (coding exon 24) of the SLC4A7 gene. This alteration results from a T to C substitution at nucleotide position 3530, causing the leucine (L) at amino acid position 1177 to be replaced by a proline (P). 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	0.18
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	.;.;T;.;.;.;.;.;.;.
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.081	D
MetaRNN	Uncertain	0.45	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.29	T
MutationAssessor	Benign	1.7	.;.;L;.;.;.;.;.;.;.
PhyloP100		4.8
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.5	.;D;D;N;D;D;N;D;N;D
REVEL	Uncertain	0.51
Sift	Uncertain	0.014	.;D;D;D;D;D;D;D;D;D
Sift4G	Benign	0.15	T;T;T;T;T;T;T;T;T;T
Polyphen		0.90, 0.65, 0.0010	.;.;P;P;.;.;.;.;.;B
Vest4		0.61
MutPred		0.39		.;.;Loss of helix (P = 0.0138);.;.;.;.;.;.;.;
MVP		0.24
MPC		0.84
ClinPred		0.96	D
GERP RS		5.4
Varity_R		0.59
gMVP		0.71
Mutation Taster		=35/65	disease causing

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

Other links and lift over

hg19: chr3-27424677;