chr17-81252291-C-T

Variant names:

• chr17-81252291-C-T
• rs1420622940
• NM_001037984.3:c.1849G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001037984.3(SLC38A10):​c.1849G>A​(p.Gly617Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,609,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SLC38A10 NM_001037984.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.170
• Publications: 0 publications found

Genes affected

SLC38A10 (HGNC:28237): (solute carrier family 38 member 10) Predicted to enable amino acid transmembrane transporter activity. Predicted to be involved in amino acid transmembrane transport. Predicted to act upstream of or within bone development. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036945283).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037984.3. 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
	SLC38A10	NM_001037984.3	MANE Select	c.1849G>A	p.Gly617Ser	missense	Exon 13 of 16	NP_001033073.1	Q9HBR0-1
	SLC38A10	NM_138570.4		c.1849G>A	p.Gly617Ser	missense	Exon 13 of 14	NP_612637.1	Q9HBR0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC38A10	ENST00000374759.8	TSL:5 MANE Select	c.1849G>A	p.Gly617Ser	missense	Exon 13 of 16	ENSP00000363891.3	Q9HBR0-1
	SLC38A10	ENST00000288439.9	TSL:1	c.1849G>A	p.Gly617Ser	missense	Exon 13 of 14	ENSP00000288439.5	Q9HBR0-2
	SLC38A10	ENST00000947966.1		c.1849G>A	p.Gly617Ser	missense	Exon 13 of 18	ENSP00000618025.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152214 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000813 AC: 2 AN: 246122 AF XY: 0.00000745

Gnomad AFR exome AF: 0.0000657

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: 0.00000905

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1457726 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724658

African (AFR) AF: 0.0000299 AC: 1 AN: 33400

American (AMR) AF: 0.00 AC: 0 AN: 44500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.00 AC: 0 AN: 86106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52064

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5756

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109990

Other (OTH) AF: 0.00 AC: 0 AN: 60200

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152214 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74364

African (AFR) AF: 0.0000241 AC: 1 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.075
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.8
DANN	Benign	0.64
DEOGEN2	Benign	0.0012	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.17
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.46	N
REVEL	Benign	0.040
Sift	Benign	0.67	T
Sift4G	Benign	0.69	T
Polyphen		0.0080	B
Vest4		0.033
MutPred		0.34		Loss of relative solvent accessibility (P = 0.0676)
MVP		0.048
MPC		0.12
ClinPred		0.042	T
GERP RS		2.6
PromoterAI		-0.0072	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.036
gMVP		0.19
Mutation Taster		=97/3	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: rs1420622940; hg19: chr17-79226091;