rs11984297

Positions:

• chr7-27196874-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4288 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXA13	NM_000522.5	c.*1324A>C		3_prime_UTR_variant	2/2	ENST00000649031.1	NP_000513.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXA13	ENST00000649031	c.*1324A>C		3_prime_UTR_variant	2/2		NM_000522.5	ENSP00000497112.1

Frequencies

GnomAD3 genomes AF: 0.0282 AC: 4290 AN: 152230 Hom.: 81 Cov.: 33

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.: 10 Cov.: 0 AF XY: 0.0218 AC XY: 257 AN XY: 11806

Gnomad4 AFR exome AF: 0.0168

Gnomad4 AMR exome AF: 0.0213

Gnomad4 ASJ exome AF: 0.00765

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0383

Gnomad4 NFE exome AF: 0.0330

Gnomad4 OTH exome AF: 0.0273

GnomAD4 genome AF: 0.0281 AC: 4288 AN: 152348 Hom.: 81 Cov.: 33 AF XY: 0.0278 AC XY: 2072 AN XY: 74500

Gnomad4 AFR AF: 0.0188

Gnomad4 AMR AF: 0.0231

Gnomad4 ASJ AF: 0.00980

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.0453

Gnomad4 NFE AF: 0.0367

Gnomad4 OTH AF: 0.0355

Alfa AF: 0.0339 Hom.: 111

Bravo AF: 0.0263

Asia WGS AF: 0.00318 AC: 11 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	15
DANN	Benign	0.83

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

Other links and lift over

dbSNP: rs11984297; hg19: chr7-27236493;