NM_152381.6:c.428G>A

Variant names:

• chr2-167135928-G-A
• rs368235986
• NM_152381.6:c.428G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152381.6(XIRP2):​c.428G>A​(p.Ser143Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000243 in 1,602,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00025 (0 hom.)
• Consequence: XIRP2 NM_152381.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.36
• Publications: 1 publications found

Genes affected

XIRP2 (HGNC:14303): (xin actin binding repeat containing 2) Enables actin filament binding activity. Predicted to be involved in actin cytoskeleton organization and heart development. Predicted to act upstream of or within cardiac muscle tissue morphogenesis; cell-cell junction organization; and ventricular septum development. Colocalizes with focal adhesion and stress fiber. [provided by Alliance of Genome Resources, Apr 2022]

XIRP2-AS1 (HGNC:40679): (XIRP2 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010282397).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152381.6. 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
	XIRP2	NM_152381.6	MANE Select	c.428G>A	p.Ser143Asn	missense	Exon 3 of 11	NP_689594.4
	XIRP2	NM_001199143.2		c.428G>A	p.Ser143Asn	missense	Exon 3 of 11	NP_001186072.1	A4UGR9-6
	XIRP2	NM_001079810.4		c.428G>A	p.Ser143Asn	missense	Exon 3 of 10	NP_001073278.1	A4UGR9-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XIRP2	ENST00000409195.6	TSL:5 MANE Select	c.428G>A	p.Ser143Asn	missense	Exon 3 of 11	ENSP00000386840.2	A4UGR9-8
	XIRP2	ENST00000409728.5	TSL:1	c.428G>A	p.Ser143Asn	missense	Exon 3 of 11	ENSP00000386619.1	A4UGR9-6
	XIRP2	ENST00000409043.5	TSL:1	c.428G>A	p.Ser143Asn	missense	Exon 3 of 10	ENSP00000386454.1	A4UGR9-4

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152116 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000312 AC: 75 AN: 240574 AF XY: 0.000351

Gnomad AFR exome AF: 0.0000665

Gnomad AMR exome AF: 0.0000627

Gnomad ASJ exome AF: 0.00412

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000469

Gnomad NFE exome AF: 0.000281

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000249 AC: 361 AN: 1449884 Hom.: 0 Cov.: 30 AF XY: 0.000255 AC XY: 184 AN XY: 721464

African (AFR) AF: 0.00 AC: 0 AN: 32880

American (AMR) AF: 0.0000472 AC: 2 AN: 42402

Ashkenazi Jewish (ASJ) AF: 0.00529 AC: 136 AN: 25716

East Asian (EAS) AF: 0.00 AC: 0 AN: 39120

South Asian (SAS) AF: 0.00 AC: 0 AN: 84556

European-Finnish (FIN) AF: 0.0000566 AC: 3 AN: 53030

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5700

European-Non Finnish (NFE) AF: 0.000168 AC: 186 AN: 1106694

Other (OTH) AF: 0.000552 AC: 33 AN: 59786

GnomAD4 genome AF: 0.000184 AC: 28 AN: 152116 Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15 AN XY: 74290

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.0000655 AC: 1 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68018

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.000519 Hom.: 0

Bravo AF: 0.000178

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.000190 AC: 23

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	0.085
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	11
DANN	Benign	0.95
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-0.83	T
PhyloP100		1.4
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.096
Sift	Benign	0.24	T
Sift4G	Benign	0.54	T
Polyphen		0.037	B
Vest4		0.13
MVP		0.12
MPC		0.020
ClinPred		0.021	T
GERP RS		1.5
PromoterAI		-0.12	Neutral
gMVP		0.014
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs368235986; hg19: chr2-167992438;