chr7-140335498-A-C

Variant names:

• chr7-140335498-A-C
• rs375656529
• NM_207113.3:c.1399T>G

Variant summary

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

The NM_207113.3(SLC37A3):​c.1399T>G​(p.Cys467Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000434 in 1,613,430 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: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000045 (0 hom.)
• Consequence: SLC37A3 NM_207113.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.41
• Publications: 0 publications found

Genes affected

SLC37A3 (HGNC:20651): (solute carrier family 37 member 3) Predicted to enable transmembrane transporter activity. Predicted to be involved in carbohydrate transport and transmembrane transport. Is integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC37A3 Gene-Disease associations (from GenCC):

• retinitis pigmentosa

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics

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=0.35154188).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207113.3. 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
	SLC37A3	NM_207113.3	MANE Select	c.1399T>G	p.Cys467Gly	missense	Exon 15 of 15	NP_996996.1	Q8NCC5-1
	SLC37A3	NM_001363373.1		c.1247T>G	p.Leu416Trp	missense	Exon 14 of 14	NP_001350302.1
	SLC37A3	NM_001287498.2		c.1351T>G	p.Cys451Gly	missense	Exon 14 of 14	NP_001274427.1	Q8NCC5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC37A3	ENST00000326232.14	TSL:1 MANE Select	c.1399T>G	p.Cys467Gly	missense	Exon 15 of 15	ENSP00000321498.9	Q8NCC5-1
	SLC37A3	ENST00000447932.6	TSL:1	c.1351T>G	p.Cys451Gly	missense	Exon 14 of 14	ENSP00000397481.2	Q8NCC5-2
	SLC37A3	ENST00000340308.7	TSL:1	c.1097T>G	p.Leu366Trp	missense	Exon 12 of 12	ENSP00000343358.3	Q8NCC5-3

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 250804 AF XY: 0.00

Gnomad AFR exome AF: 0.0000615

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: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000452 AC: 66 AN: 1461206 Hom.: 0 Cov.: 30 AF XY: 0.0000385 AC XY: 28 AN XY: 726916

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52902

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000576 AC: 64 AN: 1111864

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152224 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74364

African (AFR) AF: 0.00 AC: 0 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.0000416

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Benign	0.92
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	2.0	M
PhyloP100		4.4
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.19
Sift	Benign	0.043	D
Sift4G	Benign	0.17	T
Polyphen		0.0040	B
Vest4		0.23
MVP		0.70
MPC		0.34
ClinPred		0.27	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.34
gMVP		0.16
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs375656529; hg19: chr7-140035298;