rs3743171

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr15-65624189-A-T
• chr15-65624189-A-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004727.3(SLC24A1):​c.109A>T​(p.Thr37Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,613,544 control chromosomes in the GnomAD database, including 42,976 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (4217 hom., cov: 31)
  • Exomes 𝑓: 0.21 (38759 hom.)
• Consequence: SLC24A1 NM_004727.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• 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):

• inherited retinal dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• congenital stationary night blindness 1D

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LOC102723464 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.5433449E-6).
• BP6: Variant 15-65624189-A-T is Benign according to our data. Variant chr15-65624189-A-T is described in ClinVar as Benign. ClinVar VariationId is 259525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004727.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A1	NM_004727.3	MANE Select	c.109A>T	p.Thr37Ser	missense	Exon 2 of 10	NP_004718.1	O60721-1
	SLC24A1	NM_001301032.1		c.109A>T	p.Thr37Ser	missense	Exon 1 of 8	NP_001287961.1	O60721-2
	SLC24A1	NM_001301031.1		c.109A>T	p.Thr37Ser	missense	Exon 1 of 8	NP_001287960.1	B4E1W0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A1	ENST00000261892.11	TSL:1 MANE Select	c.109A>T	p.Thr37Ser	missense	Exon 2 of 10	ENSP00000261892.6	O60721-1
	SLC24A1	ENST00000546330.1	TSL:1	c.109A>T	p.Thr37Ser	missense	Exon 1 of 8	ENSP00000439190.1	O60721-2
	SLC24A1	ENST00000399033.8	TSL:1	c.109A>T	p.Thr37Ser	missense	Exon 1 of 8	ENSP00000381991.4	O60721-3

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30994 AN: 151842 Hom.: 4216 Cov.: 31

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.198

GnomAD2 exomes AF: 0.255 AC: 63538 AN: 249112 AF XY: 0.255

Gnomad AFR exome AF: 0.140

Gnomad AMR exome AF: 0.267

Gnomad ASJ exome AF: 0.142

Gnomad EAS exome AF: 0.737

Gnomad FIN exome AF: 0.264

Gnomad NFE exome AF: 0.182

Gnomad OTH exome AF: 0.213

GnomAD4 exome AF: 0.208 AC: 304281 AN: 1461584 Hom.: 38759 Cov.: 35 AF XY: 0.211 AC XY: 153615 AN XY: 727074

African (AFR) AF: 0.141 AC: 4736 AN: 33474

American (AMR) AF: 0.255 AC: 11401 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 3774 AN: 26134

East Asian (EAS) AF: 0.701 AC: 27841 AN: 39700

South Asian (SAS) AF: 0.326 AC: 28132 AN: 86246

European-Finnish (FIN) AF: 0.263 AC: 14027 AN: 53398

Middle Eastern (MID) AF: 0.170 AC: 981 AN: 5768

European-Non Finnish (NFE) AF: 0.180 AC: 199903 AN: 1111802

Other (OTH) AF: 0.223 AC: 13486 AN: 60368

GnomAD4 genome AF: 0.204 AC: 30999 AN: 151960 Hom.: 4217 Cov.: 31 AF XY: 0.214 AC XY: 15896 AN XY: 74256

African (AFR) AF: 0.142 AC: 5880 AN: 41450

American (AMR) AF: 0.213 AC: 3257 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 505 AN: 3470

East Asian (EAS) AF: 0.736 AC: 3787 AN: 5144

South Asian (SAS) AF: 0.341 AC: 1639 AN: 4812

European-Finnish (FIN) AF: 0.280 AC: 2955 AN: 10554

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12408 AN: 67954

Other (OTH) AF: 0.203 AC: 428 AN: 2112

Alfa AF: 0.195 Hom.: 2805

Bravo AF: 0.197

TwinsUK AF: 0.182 AC: 675

ALSPAC AF: 0.187 AC: 719

ESP6500AA AF: 0.137 AC: 523

ESP6500EA AF: 0.170 AC: 1407

ExAC AF: 0.252 AC: 30452

Asia WGS AF: 0.464 AC: 1615 AN: 3478

EpiCase AF: 0.177

EpiControl AF: 0.173

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Congenital stationary night blindness 1D (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	8.3
DANN	Benign	0.94
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.45	T
MetaRNN	Benign	0.0000025	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.040
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.14
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.069
MutPred		0.58		Loss of loop (P = 0.0128)
MPC		0.52
ClinPred		0.022	T
GERP RS		2.7
PromoterAI		0.0015	Neutral
Varity_R		0.080
gMVP		0.12
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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; COSMIC: COSV107245586; COSMIC: COSV107245586;