chr3-39184302-A-T

Position:

• chr3-39184302-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_194293.4(XIRP1):​c.5144T>A​(p.Val1715Asp) 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: XIRP1 NM_194293.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0520

Genes affected

XIRP1 (HGNC:14301): (xin actin binding repeat containing 1) The protein encoded by this gene is a striated muscle protein and belongs to the Xin actin-binding repeat-containing protein (XIRP) family. The protein functions to protect actin filaments during depolymerization. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10831311).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XIRP1	NM_194293.4	c.5144T>A	p.Val1715Asp	missense_variant	2/2	ENST00000340369.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XIRP1	ENST00000340369.4	c.5144T>A	p.Val1715Asp	missense_variant	2/2	1	NM_194293.4	A2
XIRP1	ENST00000421646.1	c.1193T>A	p.Val398Asp	missense_variant	2/2	1
XIRP1	ENST00000396251.1	c.*1351T>A		3_prime_UTR_variant	3/3	1		P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Apr 09, 2024

The c.5144T>A (p.V1715D) alteration is located in exon 2 (coding exon 1) of the XIRP1 gene. This alteration results from a T to A substitution at nucleotide position 5144, causing the valine (V) at amino acid position 1715 to be replaced by an aspartic acid (D). 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	0.12
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	1.7
DANN	Benign	0.79
DEOGEN2	Benign	0.098	T;.
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.51	T;T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.016
Sift	Uncertain	0.0050	D;D
Sift4G	Benign	0.63	T;D
Polyphen		0.70	P;.
Vest4		0.27
MutPred		0.24		Loss of loop (P = 0.0128);.;
MVP		0.22
MPC		0.14
ClinPred		0.40	T
GERP RS		0.97
Varity_R		0.21
gMVP		0.11

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-39225793;