7-27199445-C-A

Position:

chr7-27199445-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000522.5(HOXA13):c.633G>T(p.Met211Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000829 in 1,613,608 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00044 ( 6 hom. )

Consequence

HOXA13
NM_000522.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.63

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:

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]

HOTTIP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008342475).

BP6

Variant 7-27199445-C-A is Benign according to our data. Variant chr7-27199445-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 376765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000443 (647/1461320) while in subpopulation AFR AF= 0.0169 (565/33476). AF 95% confidence interval is 0.0157. There are 6 homozygotes in gnomad4_exome. There are 243 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 691 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXA13	NM_000522.5 linkuse as main transcript	c.633G>T	p.Met211Ile	missense_variant	1/2	ENST00000649031.1	NP_000513.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
HOXA13	ENST00000649031.1 linkuse as main transcript	c.633G>T	p.Met211Ile	missense_variant	1/2		NM_000522.5	ENSP00000497112	P1
HOTTIP	ENST00000421733.1 linkuse as main transcript	n.167+704C>A		intron_variant, non_coding_transcript_variant		5
HOTTIP	ENST00000605136.6 linkuse as main transcript	n.86+115C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00455

AC:

692

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0160

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00122

AC:

303

AN:

247510

Hom.:

AF XY:

0.000831

AC XY:

112

AN XY:

134758

show subpopulations

Gnomad AFR exome

AF:

0.0174

Gnomad AMR exome

AF:

0.000697

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000443

AC:

647

AN:

1461320

Hom.:

Cov.:

AF XY:

0.000334

AC XY:

243

AN XY:

726994

show subpopulations

Gnomad4 AFR exome

AF:

0.0169

Gnomad4 AMR exome

AF:

0.000649

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.000745

GnomAD4 genome

AF:

0.00454

AC:

691

AN:

152288

Hom.:

Cov.:

AF XY:

0.00432

AC XY:

322

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0159

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00105

Hom.:

Bravo

AF:

0.00509

ESP6500AA

AF:

0.0143

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00136

AC:

165

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jan 05, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.43

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.57

D;D

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

.;D

MetaRNN

Benign

0.0083

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Pathogenic

3.0

M;M

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-2.9

.;D

REVEL

Benign

0.17

Sift

Benign

0.084

.;T

Sift4G

Benign

0.10

.;T

Polyphen

0.59

P;P

Vest4

0.57

MutPred

0.24

Loss of disorder (P = 0.0665);Loss of disorder (P = 0.0665);

MVP

0.42

ClinPred

0.046

GERP RS

3.1

Varity_R

0.36

gMVP

0.47

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