Variant 12-49089936-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_021044.4(DHH):c.1114G>A(p.Gly372Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000629 in 1,430,946 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

DHH
NM_021044.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.18

Variant links:

Genes affected

DHH (HGNC:2865): (desert hedgehog signaling molecule) This gene encodes a member of the hedgehog family. The hedgehog gene family encodes signaling molecules that play an important role in regulating morphogenesis. This protein is predicted to be made as a precursor that is autocatalytically cleaved; the N-terminal portion is soluble and contains the signalling activity while the C-terminal portion is involved in precursor processing. More importantly, the C-terminal product covalently attaches a cholesterol moiety to the N-terminal product, restricting the N-terminal product to the cell surface and preventing it from freely diffusing throughout the organism. Defects in this protein have been associated with partial gonadal dysgenesis (PGD) accompanied by minifascicular polyneuropathy. This protein may be involved in both male gonadal differentiation and perineurial development. [provided by RefSeq, May 2010]

DHH links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHH	NM_021044.4 link	c.1114G>A	p.Gly372Ser	missense_variant	3/3	ENST00000649637.2	NP_066382.1	O43323
DHH	XM_017019380.2 link	c.973G>A	p.Gly325Ser	missense_variant	3/3		XP_016874869.1
DHH	XM_017019381.2 link	c.772G>A	p.Gly258Ser	missense_variant	3/3		XP_016874870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHH	ENST00000649637.2 link	c.1114G>A	p.Gly372Ser	missense_variant	3/3		NM_021044.4	ENSP00000497483.1		O43323

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000522

AC:

AN:

191412

Hom.:

AF XY:

0.00

AC XY:

AN XY:

104224

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000121

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000629

AC:

AN:

1430946

Hom.:

Cov.:

AF XY:

0.00000564

AC XY:

AN XY:

709128

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000820

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 11, 2024

The c.1114G>A (p.G372S) alteration is located in exon 3 (coding exon 3) of the DHH gene. This alteration results from a G to A substitution at nucleotide position 1114, causing the glycine (G) at amino acid position 372 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Uncertain

0.62

D;D

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.66

.;T

M_CAP

Pathogenic

0.56

MetaRNN

Uncertain

0.47

T;T

MetaSVM

Pathogenic

0.93

MutationAssessor

Benign

0.34

N;N

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.19

.;N

REVEL

Uncertain

0.38

Sift

Benign

1.0

.;T

Sift4G

Benign

0.68

.;T

Polyphen

0.96

D;D

Vest4

0.26

MutPred

0.44

Gain of catalytic residue at V375 (P = 0);Gain of catalytic residue at V375 (P = 0);

MVP

0.97

MPC

1.0

ClinPred

0.20

GERP RS

4.8

Varity_R

0.087

gMVP

0.59

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