Variant 5-141572026-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005219.5(DIAPH1):c.2373C>G(p.Asp791Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D791D) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DIAPH1
NM_005219.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.300

Variant links:

Genes affected

DIAPH1 (HGNC:2876): (diaphanous related formin 1) This gene is a homolog of the Drosophila diaphanous gene, and has been linked to autosomal dominant, fully penetrant, nonsyndromic sensorineural progressive low-frequency hearing loss. Actin polymerization involves proteins known to interact with diaphanous protein in Drosophila and mouse. It has therefore been speculated that this gene may have a role in the regulation of actin polymerization in hair cells of the inner ear. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

DIAPH1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.079061866).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DIAPH1	NM_005219.5 linkuse as main transcript	c.2373C>G	p.Asp791Glu	missense_variant	17/28	ENST00000389054.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIAPH1	ENST00000389054.8 linkuse as main transcript	c.2373C>G	p.Asp791Glu	missense_variant	17/28	5	NM_005219.5	A2	O60610-1
DIAPH1	ENST00000518047.5 linkuse as main transcript	c.2346C>G	p.Asp782Glu	missense_variant	16/27	5		P4	O60610-3
DIAPH1	ENST00000647433.1 linkuse as main transcript	c.2373C>G	p.Asp791Glu	missense_variant	17/29			A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249570

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135404

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461450

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727078

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.62

DEOGEN2

Benign

0.048

T;.;T;.;T;.

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.60

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.73

T;T;T;T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.079

T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.69

N;.;.;.;.;.

MutationTaster

Benign

0.95

D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

0.52

N;.;.;N;N;N

REVEL

Benign

0.17

Sift

Benign

1.0

T;.;.;T;T;T

Sift4G

Benign

1.0

T;.;T;T;T;T

Polyphen

0.020

B;.;.;.;.;.

Vest4

0.10

MutPred

0.40

Loss of ubiquitination at K786 (P = 0.0747);Loss of ubiquitination at K786 (P = 0.0747);.;.;Loss of ubiquitination at K786 (P = 0.0747);.;

MVP

0.56

MPC

0.57

ClinPred

0.056

GERP RS

0.096

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.036

gMVP

0.25

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over