17-81246221-C-A

Variant names:

• chr17-81246221-C-A
• NM_001037984.3:c.2695G>T

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.2695G>T​(p.Val899Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC38A10 NM_001037984.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.259
• 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: 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=0.07568073).

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.2695G>T	p.Val899Leu	missense	Exon 16 of 16	NP_001033073.1	Q9HBR0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC38A10	ENST00000374759.8	TSL:5 MANE Select	c.2695G>T	p.Val899Leu	missense	Exon 16 of 16	ENSP00000363891.3	Q9HBR0-1
	SLC38A10	ENST00000539643.1	TSL:1	n.771G>T		non_coding_transcript_exon	Exon 2 of 2
	SLC38A10	ENST00000947966.1		c.2866G>T	p.Val956Leu	missense	Exon 18 of 18	ENSP00000618025.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 77

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	SLC38A10-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	8.9
DANN	Benign	0.97
DEOGEN2	Benign	0.0065	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.26
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.096
Sift	Benign	0.34	T
Sift4G	Benign	0.24	T
Polyphen		0.012	B
Vest4		0.073
MutPred		0.47		Loss of sheet (P = 0.0315)
MVP		0.25
MPC		0.13
ClinPred		0.17	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.095
gMVP		0.10

Splicing

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

Other links and lift over

hg19: chr17-79220021;