3-27395072-T-C

Variant names:

• chr3-27395072-T-C
• rs1221694036
• NM_001321103.2:c.2747A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001321103.2(SLC4A7):​c.2747A>G​(p.Asp916Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D916V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC4A7 NM_001321103.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.447
• 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07742751).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A7	NM_001321103.2	c.2747A>G	p.Asp916Gly	missense_variant	Exon 19 of 26	ENST00000454389.6	NP_001308032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A7	ENST00000454389.6	c.2747A>G	p.Asp916Gly	missense_variant	Exon 19 of 26	1	NM_001321103.2	ENSP00000390394.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Benign	0.91
DEOGEN2	Benign	0.16	.;.;T;.;.;.;.;.;.;.;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.18	N
LIST_S2	Uncertain	0.87	D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.077	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.25	.;.;N;.;.;.;.;.;.;.;.
PhyloP100		0.45
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.3	.;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.28
Sift	Benign	0.90	.;T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.70	T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.0	.;.;B;B;.;.;.;.;.;B;.
Vest4		0.12
MutPred		0.35		.;.;Loss of glycosylation at S903 (P = 0.0163);.;.;.;.;.;.;.;.;
MVP		0.082
MPC		0.38
ClinPred		0.26	T
GERP RS		6.1
Varity_R		0.059
gMVP		0.49
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

dbSNP: rs1221694036; hg19: chr3-27436563;