Variant 7-27198363-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_000522.5(HOXA13):c.1002A>G(p.Leu334=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00305 in 1,614,234 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0031 ( 15 hom. )

Consequence

HOXA13
NM_000522.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.57

Variant links:

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]

HOXA13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 7-27198363-T-C is Benign according to our data. Variant chr7-27198363-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 713824.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-27198363-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.57 with no splicing effect.

BS2

High AC in GnomAd4 at 317 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOXA13	NM_000522.5 linkuse as main transcript	c.1002A>G	p.Leu334=	synonymous_variant	2/2	ENST00000649031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOXA13	ENST00000649031.1 linkuse as main transcript	c.1002A>G	p.Leu334=	synonymous_variant	2/2		NM_000522.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00208

AC:

317

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00326

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00182

AC:

458

AN:

251476

Hom.:

AF XY:

0.00175

AC XY:

238

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00153

Gnomad ASJ exome

AF:

0.000694

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000817

Gnomad FIN exome

AF:

0.00129

Gnomad NFE exome

AF:

0.00291

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00315

AC:

4601

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00302

AC XY:

2195

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.00154

Gnomad4 ASJ exome

AF:

0.000612

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00130

Gnomad4 FIN exome

AF:

0.00137

Gnomad4 NFE exome

AF:

0.00371

Gnomad4 OTH exome

AF:

0.00321

GnomAD4 genome

AF:

0.00208

AC:

317

AN:

152350

Hom.:

Cov.:

AF XY:

0.00226

AC XY:

168

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00346

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.00326

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00265

Hom.:

Bravo

AF:

0.00194

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00344

EpiControl

AF:

0.00338

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 20, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	HOXA13: BP4, BP7 -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

8.7

DANN

Benign

0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over