17-81252258-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001037984.3(SLC38A10):​c.1882G>C​(p.Gly628Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000189 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SLC38A10 NM_001037984.3 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08169088).

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

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152246 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

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: 0.00000431 AC: 1 AN: 232080 AF XY: 0.00

Gnomad AFR exome AF: 0.0000670

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1438762 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 713872

African (AFR) AF: 0.00 AC: 0 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: 0.00 AC: 0 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: 0.00 AC: 0 AN: 1100466

Other (OTH) AF: 0.00 AC: 0 AN: 59250

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152246 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74384

African (AFR) AF: 0.0000482 AC: 2 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: 0.0000257 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000825 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.29
DANN	Benign	0.47
DEOGEN2	Benign	0.0063	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0085	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.082	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		0.089	T
GERP RS		-1.5
PromoterAI		0.023	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2
Varity_R		0.058
gMVP		0.15

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;