17-81252291-C-A

Variant names:

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

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>T​(p.Gly617Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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. G617S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC38A10 NM_001037984.3 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.06387761).

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>T	p.Gly617Cys	missense	Exon 13 of 16	NP_001033073.1	Q9HBR0-1
	SLC38A10	NM_138570.4		c.1849G>T	p.Gly617Cys	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>T	p.Gly617Cys	missense	Exon 13 of 16	ENSP00000363891.3	Q9HBR0-1
	SLC38A10	ENST00000288439.9	TSL:1	c.1849G>T	p.Gly617Cys	missense	Exon 13 of 14	ENSP00000288439.5	Q9HBR0-2
	SLC38A10	ENST00000947966.1		c.1849G>T	p.Gly617Cys	missense	Exon 13 of 18	ENSP00000618025.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457726 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724658

African (AFR) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 5756

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

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.8
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.17
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.042
Sift	Benign	0.066	T
Sift4G	Benign	0.075	T
Polyphen		0.22	B
Vest4		0.16
MutPred		0.39		Loss of relative solvent accessibility (P = 0.0186)
MVP		0.17
MPC		0.21
ClinPred		0.25	T
GERP RS		2.6
PromoterAI		-0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.11
gMVP		0.24
Mutation Taster		=98/2	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;