rs565588237

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001164405.2(BHLHA9):c.74G>A(p.Gly25Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00029 in 1,301,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

BHLHA9
NM_001164405.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.811

Publications

0 publications found

Variant links:

Genes affected

BHLHA9 (HGNC:35126): (basic helix-loop-helix family member a9) This gene is a member of the basic helix-loop-helix family. The encoded protein is a transcription factor involved in limb development. Mutations in this gene have been associated with mesoaxial synostotic syndactyly Malik-Percin type (MSSD). Copy number variation of a locus containing this gene has been linked to a form of split-hand/foot malformation with long bone deficiency (SHFLD3). [provided by RefSeq, Mar 2015]

BHLHA9 Gene-Disease associations (from GenCC):

mesoaxial synostotic syndactyly with phalangeal reduction
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
tibial aplasia-ectrodactyly syndrome
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
Camptosynpolydactyly, complex
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
split-hand/foot malformation with long bone deficiency 1
Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

BHLHA9 links:

ENSG00000300095 (HGNC:):

ENSG00000300095 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07134196).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164405.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BHLHA9	NM_001164405.2	MANE Select	c.74G>A	p.Gly25Asp	missense	Exon 1 of 1	NP_001157877.1	Q7RTU4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BHLHA9	ENST00000391429.2	TSL:6 MANE Select	c.74G>A	p.Gly25Asp	missense	Exon 1 of 1	ENSP00000375248.1	Q7RTU4
ENSG00000300095	ENST00000768751.1		n.-133C>T		upstream_gene	N/A
ENSG00000300095	ENST00000768752.1		n.-136C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD4 exome

AF:

0.000323

AC:

371

AN:

1148856

Hom.:

Cov.:

AF XY:

0.000314

AC XY:

173

AN XY:

550566

show subpopulations

African (AFR)

AF:

0.0000862

AC:

AN:

23208

American (AMR)

AF:

0.00

AC:

AN:

8622

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15524

East Asian (EAS)

AF:

0.00

AC:

AN:

26880

South Asian (SAS)

AF:

0.00

AC:

AN:

35332

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3396

European-Non Finnish (NFE)

AF:

0.000379

AC:

365

AN:

963248

Other (OTH)

AF:

0.0000850

AC:

AN:

47042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41556

American (AMR)

AF:

0.00

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

67988

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.0000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Benign

-0.30

CADD

Benign

5.3

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.013

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.32

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.071

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

0.55

PhyloP100

-0.81

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.3

REVEL

Benign

0.21

Sift

Benign

0.071

Sift4G

Benign

0.35

Vest4

0.071

MutPred

0.21

Loss of catalytic residue at G25 (P = 0.0511)

MVP

0.17

ClinPred

0.14

GERP RS

0.43

PromoterAI

-0.0074

Neutral

(source)

Varity_R

0.11

gMVP

0.28

Mutation Taster

=95/5

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over