Genetic Variant HOXA13:c.*1324A>C (chr7-27196874-T-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBS1BS2

The NM_000522.5(HOXA13):c.*1324A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 178,000 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.028 ( 81 hom., cov: 33)

Exomes 𝑓: 0.023 ( 10 hom. )

Consequence

HOXA13
NM_000522.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.81

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

hand-foot-genital syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics
Guttmacher syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

HOXA13 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0281 (4288/152348) while in subpopulation NFE AF = 0.0367 (2498/68040). AF 95% confidence interval is 0.0355. There are 81 homozygotes in GnomAd4. There are 2072 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 4288 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXA13	NM_000522.5 link	c.*1324A>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000649031.1	NP_000513.2	P31271Q6DI00

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXA13	ENST00000649031.1 link	c.*1324A>C		3_prime_UTR_variant	Exon 2 of 2		NM_000522.5	ENSP00000497112.1		P31271

Frequencies

GnomAD3 genomes

AF:

0.0282

AC:

4290

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0189

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.0232

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0453

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0367

Gnomad OTH

AF:

0.0359

GnomAD4 exome

AF:

0.0230

AC:

590

AN:

25652

Hom.:

Cov.:

AF XY:

0.0218

AC XY:

257

AN XY:

11806

show subpopulations

African (AFR)

AF:

0.0168

AC:

AN:

834

American (AMR)

AF:

0.0213

AC:

AN:

564

Ashkenazi Jewish (ASJ)

AF:

0.00765

AC:

AN:

1568

East Asian (EAS)

AF:

0.00

AC:

AN:

5432

South Asian (SAS)

AF:

0.00

AC:

AN:

206

European-Finnish (FIN)

AF:

0.0383

AC:

AN:

444

Middle Eastern (MID)

AF:

0.0203

AC:

AN:

148

European-Non Finnish (NFE)

AF:

0.0330

AC:

476

AN:

14404

Other (OTH)

AF:

0.0273

AC:

AN:

2052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

110

137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0281

AC:

4288

AN:

152348

Hom.:

Cov.:

AF XY:

0.0278

AC XY:

2072

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.0188

AC:

782

AN:

41588

American (AMR)

AF:

0.0231

AC:

354

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00980

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000621

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0453

AC:

481

AN:

10610

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0367

AC:

2498

AN:

68040

Other (OTH)

AF:

0.0355

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

222

444

666

888

1110

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0332

Hom.:

144

Bravo

AF:

0.0263

Asia WGS

AF:

0.00318

AC:

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

1.8

Mutation Taster

=100/0

polymorphism

(source)

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

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chr7-27196874-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over