19-33210598-T-C

Position:

• chr19-33210598-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019849.3(SLC7A10):​c.1132A>G​(p.Ile378Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,459,482 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: SLC7A10 NM_019849.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.96

Genes affected

SLC7A10 (HGNC:11058): (solute carrier family 7 member 10) SLC7A10, in association with 4F2HC (SLC3A2; MIM 158070), mediates high-affinity transport of D-serine and several other neutral amino acids (Nakauchi et al., 2000 [PubMed 10863037]).[supplied by OMIM, Mar 2008]

SLC7A10 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A10	NM_019849.3	c.1132A>G	p.Ile378Val	missense_variant	9/11	ENST00000253188.8	NP_062823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A10	ENST00000253188.8	c.1132A>G	p.Ile378Val	missense_variant	9/11	1	NM_019849.3	ENSP00000253188.2
SLC7A10	ENST00000590036.5	n.1035A>G		non_coding_transcript_exon_variant	8/10	5		ENSP00000465421.1
SLC7A10	ENST00000590490.1	n.907A>G		non_coding_transcript_exon_variant	2/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000685 AC: 10 AN: 1459482 Hom.: 0 Cov.: 33 AF XY: 0.00000551 AC XY: 4 AN XY: 726038

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 05, 2022

The c.1132A>G (p.I378V) alteration is located in exon 9 (coding exon 9) of the SLC7A10 gene. This alteration results from a A to G substitution at nucleotide position 1132, causing the isoleucine (I) at amino acid position 378 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.084	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Uncertain	0.39	D
MutationAssessor	Benign	0.91	L
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.24	N
REVEL	Uncertain	0.56
Sift	Benign	0.041	D
Sift4G	Benign	0.52	T
Polyphen		0.65	P
Vest4		0.59
MutPred		0.45		Gain of catalytic residue at I378 (P = 0.0219);
MVP		0.90
MPC		0.58
ClinPred		0.83	D
GERP RS		5.4
Varity_R		0.20
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1974523016; hg19: chr19-33701504;