19-51341489-A-T

Variant names:

• chr19-51341489-A-T
• rs748068902
• NM_001163922.3:c.559T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001163922.3(VSIG10L):​c.559T>A​(p.Ser187Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,397,948 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. S187P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: VSIG10L NM_001163922.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236
• Publications: 0 publications found

Genes affected

VSIG10L (HGNC:27111): (V-set and immunoglobulin domain containing 10 like) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

VSIG10L-AS1 (HGNC:55282): (VSIG10L antisense RNA 1)

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=0.039262176).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001163922.3. 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
	VSIG10L	NM_001163922.3	MANE Select	c.559T>A	p.Ser187Thr	missense	Exon 2 of 10	NP_001157394.1	Q86VR7-1
	VSIG10L-AS1	NR_186316.1		n.807+315A>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSIG10L	ENST00000335624.5	TSL:5 MANE Select	c.559T>A	p.Ser187Thr	missense	Exon 2 of 10	ENSP00000335623.3	Q86VR7-1
	VSIG10L	ENST00000915571.1		c.559T>A	p.Ser187Thr	missense	Exon 2 of 11	ENSP00000585630.1
	VSIG10L-AS1	ENST00000594311.1	TSL:5	n.132+315A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1397948 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 689444

African (AFR) AF: 0.00 AC: 0 AN: 31460

American (AMR) AF: 0.00 AC: 0 AN: 35444

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25122

East Asian (EAS) AF: 0.00 AC: 0 AN: 35728

South Asian (SAS) AF: 0.00 AC: 0 AN: 79086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078288

Other (OTH) AF: 0.0000173 AC: 1 AN: 57902

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.4
DANN	Benign	0.85
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.24
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.0090
Sift	Benign	0.59	T
Sift4G	Benign	0.27	T
Polyphen		0.055	B
Vest4		0.15
MutPred		0.20		Loss of loop (P = 0.1258)
MVP		0.030
ClinPred		0.049	T
GERP RS		-0.20
Varity_R		0.058
gMVP		0.12
Mutation Taster		=99/1	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: rs748068902; hg19: chr19-51844743;