chr17-81252258-C-T

Variant names:

• chr17-81252258-C-T
• rs780284908
• NM_001037984.3:c.1882G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001037984.3(SLC38A10):​c.1882G>A​(p.Gly628Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000352 in 1,591,008 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 0.00015 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: SLC38A10 NM_001037984.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.156
• Publications: 1 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.057602197).

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.1882G>A	p.Gly628Arg	missense	Exon 13 of 16	NP_001033073.1	Q9HBR0-1
	SLC38A10	NM_138570.4		c.1882G>A	p.Gly628Arg	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.1882G>A	p.Gly628Arg	missense	Exon 13 of 16	ENSP00000363891.3	Q9HBR0-1
	SLC38A10	ENST00000288439.9	TSL:1	c.1882G>A	p.Gly628Arg	missense	Exon 13 of 14	ENSP00000288439.5	Q9HBR0-2
	SLC38A10	ENST00000947966.1		c.1882G>A	p.Gly628Arg	missense	Exon 13 of 18	ENSP00000618025.1

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152246 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000555

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: 0.0000560 AC: 13 AN: 232080 AF XY: 0.0000788

Gnomad AFR exome AF: 0.000201

Gnomad AMR exome AF: 0.0000313

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000229 AC: 33 AN: 1438762 Hom.: 0 Cov.: 31 AF XY: 0.0000322 AC XY: 23 AN XY: 713872

African (AFR) AF: 0.000306 AC: 10 AN: 32638

American (AMR) AF: 0.0000240 AC: 1 AN: 41720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24938

East Asian (EAS) AF: 0.00 AC: 0 AN: 39372

South Asian (SAS) AF: 0.000214 AC: 18 AN: 84046

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50672

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5660

European-Non Finnish (NFE) AF: 9.09e-7 AC: 1 AN: 1100466

Other (OTH) AF: 0.0000506 AC: 3 AN: 59250

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152246 Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10 AN XY: 74384

African (AFR) AF: 0.000555 AC: 23 AN: 41462

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000257 Hom.: 0

Bravo AF: 0.000185

ExAC AF: 0.0000660 AC: 8

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	0.12
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	1.2
DANN	Benign	0.55
DEOGEN2	Benign	0.0063	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.16
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.091
Sift	Benign	0.13	T
Sift4G	Benign	0.41	T
Polyphen		0.0060	B
Vest4		0.12
MutPred		0.28		Gain of solvent accessibility (P = 0.019)
MVP		0.29
MPC		0.48
ClinPred		0.045	T
GERP RS		-1.5
PromoterAI		-0.0047	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2
Varity_R		0.058
gMVP		0.15
Mutation Taster		=91/9	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: rs780284908; hg19: chr17-79226058; COSMIC: COSV104605755; COSMIC: COSV104605755;