rs1362954246

Variant names:

• chr7-27199919-G-A
• rs1362954246
• NM_000522.5:c.159C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-27199919-G-A
• chr7-27199919-G-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000522.5(HOXA13):​c.159C>T​(p.Ala53Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000284 in 1,056,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A53A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: HOXA13 NM_000522.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.851
• Publications: 0 publications found

Genes affected

HOXA13 (HGNC:5102): (homeobox A13) In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. Expansion of a polyalanine tract in the encoded protein can cause hand-foot-uterus syndrome, also known as hand-foot-genital syndrome. [provided by RefSeq, Jul 2008]

HOTTIP (HGNC:37461): (HOXA distal transcript antisense RNA) This gene produces a long RNA in antisense to the HOXA gene cluster. This transcript may regulate expression of HOXA genes in cis. This gene is upregulated in tumors and is implicated in the promotion of cell proliferation. [provided by RefSeq, Dec 2017]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=-0.851 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000522.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXA13	NM_000522.5	MANE Select	c.159C>T	p.Ala53Ala	synonymous	Exon 1 of 2	NP_000513.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXA13	ENST00000649031.1	MANE Select	c.159C>T	p.Ala53Ala	synonymous	Exon 1 of 2	ENSP00000497112.1
	HOTTIP	ENST00000421733.1	TSL:5	n.168-704G>A		intron	N/A
	HOTTIP	ENST00000605136.7	TSL:2	n.92+589G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000284 AC: 3 AN: 1056630 Hom.: 0 Cov.: 20 AF XY: 0.00000393 AC XY: 2 AN XY: 508646

African (AFR) AF: 0.0000477 AC: 1 AN: 20982

American (AMR) AF: 0.00 AC: 0 AN: 14588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15016

East Asian (EAS) AF: 0.00 AC: 0 AN: 18870

South Asian (SAS) AF: 0.00 AC: 0 AN: 35738

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2750

European-Non Finnish (NFE) AF: 0.00000226 AC: 2 AN: 884056

Other (OTH) AF: 0.00 AC: 0 AN: 39224

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	13
DANN	Benign	0.93
PhyloP100		-0.85
PromoterAI		-0.0090	Neutral
Mutation Taster		=100/0	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: rs1362954246; hg19: chr7-27239538;