rs752601692

Variant names:

• chrX-30560084-A-G
• rs752601692
• NM_025159.3:c.272T>C

Variant summary

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

The NM_025159.3(TASL):​c.272T>C​(p.Val91Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000331 in 1,209,975 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: TASL NM_025159.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.05
• Publications: 0 publications found

Genes affected

TASL (HGNC:25667): (TLR adaptor interacting with endolysosomal SLC15A4) Involved in positive regulation of innate immune response; positive regulation of toll-like receptor signaling pathway; and regulation of lysosomal lumen pH. Located in endolysosome membrane. [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=0.16846728).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025159.3. 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
	TASL	NM_025159.3	MANE Select	c.272T>C	p.Val91Ala	missense	Exon 3 of 3	NP_079435.1	Q9HAI6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TASL	ENST00000378962.4	TSL:1 MANE Select	c.272T>C	p.Val91Ala	missense	Exon 3 of 3	ENSP00000368245.3	Q9HAI6
	TASL	ENST00000955826.1		c.272T>C	p.Val91Ala	missense	Exon 3 of 3	ENSP00000625885.1
	TASL	ENST00000955827.1		c.272T>C	p.Val91Ala	missense	Exon 2 of 2	ENSP00000625886.1

Frequencies

GnomAD3 genomes AF: 0.0000178 AC: 2 AN: 112297 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000647

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: 0.0000110 AC: 2 AN: 182307 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000731

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: 0.00000182 AC: 2 AN: 1097678 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 363058

African (AFR) AF: 0.00 AC: 0 AN: 26397

American (AMR) AF: 0.0000568 AC: 2 AN: 35185

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19348

East Asian (EAS) AF: 0.00 AC: 0 AN: 30204

South Asian (SAS) AF: 0.00 AC: 0 AN: 54003

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4133

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841836

Other (OTH) AF: 0.00 AC: 0 AN: 46064

GnomAD4 genome AF: 0.0000178 AC: 2 AN: 112297 Hom.: 0 Cov.: 23 AF XY: 0.0000290 AC XY: 1 AN XY: 34445

African (AFR) AF: 0.0000647 AC: 2 AN: 30925

American (AMR) AF: 0.00 AC: 0 AN: 10568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3585

South Asian (SAS) AF: 0.00 AC: 0 AN: 2689

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6157

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53283

Other (OTH) AF: 0.00 AC: 0 AN: 1515

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.023	T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		3.0
PROVEAN	Benign	0.34	N
REVEL	Benign	0.15
Sift	Benign	0.25	T
Sift4G	Benign	0.38	T
Polyphen		0.94	P
Vest4		0.068
MutPred		0.12		Gain of relative solvent accessibility (P = 0.0082)
MVP		0.76
MPC		0.27
ClinPred		0.25	T
GERP RS		5.3
Varity_R		0.12
gMVP		0.17
Mutation Taster		=84/16	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: rs752601692; hg19: chrX-30578201;