15-65624189-A-C

Variant names:

• chr15-65624189-A-C
• rs3743171
• NM_004727.3:c.109A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004727.3(SLC24A1):​c.109A>C​(p.Thr37Pro) 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. 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. T37S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLC24A1 NM_004727.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400
• Publications: 41 publications found

Genes affected

SLC24A1 (HGNC:10975): (solute carrier family 24 member 1) This gene encodes a member of the potassium-dependent sodium/calcium exchanger protein family. The encoded protein plays an important role in sodium/calcium exchange in retinal rod and cone photoreceptors by mediating the extrusion of one calcium ion and one potassium ion in exchange for four sodium ions. Mutations in this gene may play a role in congenital stationary night blindness. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

SLC24A1 Gene-Disease associations (from GenCC):

• congenital stationary night blindness 1D

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• congenital stationary night blindness

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LOC102723464 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3496101).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A1	NM_004727.3	c.109A>C	p.Thr37Pro	missense_variant	Exon 2 of 10	ENST00000261892.11	NP_004718.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC24A1	ENST00000261892.11	c.109A>C	p.Thr37Pro	missense_variant	Exon 2 of 10	1	NM_004727.3	ENSP00000261892.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.033	T;T;.;.;.;.
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.74	T;T;T;T;.;T
M_CAP	Uncertain	0.097	D
MetaRNN	Benign	0.35	T;T;T;T;T;T
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.0	.;M;M;.;M;M
PhyloP100		0.040
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.6	D;D;D;N;D;D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0010	D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		1.0	D;D;.;.;.;D
Vest4		0.47
MutPred		0.65		Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);
MVP		0.83
MPC		0.83
ClinPred		0.66	D
GERP RS		2.7
PromoterAI		0.0045	Neutral
Varity_R		0.39
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3743171; hg19: chr15-65916527;