Variant rs727502964 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005219.5(DIAPH1):c.128G>T(p.Arg43Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,230 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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: 6.01

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DIAPH1	NM_005219.5 linkuse as main transcript	c.128G>T	p.Arg43Leu	missense_variant	2/28	ENST00000389054.8	NP_005210.3
DIAPH1	NM_001314007.2 linkuse as main transcript	c.128G>T	p.Arg43Leu	missense_variant	2/29		NP_001300936.1
DIAPH1	XM_047416885.1 linkuse as main transcript	c.62G>T	p.Arg21Leu	missense_variant	2/28		XP_047272841.1
DIAPH1	NM_001079812.3 linkuse as main transcript	c.118-1043G>T		intron_variant			NP_001073280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIAPH1	ENST00000389054.8 linkuse as main transcript	c.128G>T	p.Arg43Leu	missense_variant	2/28	5	NM_005219.5	ENSP00000373706	A2	O60610-1
DIAPH1	ENST00000647433.1 linkuse as main transcript	c.128G>T	p.Arg43Leu	missense_variant	2/29			ENSP00000494675	A2
DIAPH1	ENST00000518047.5 linkuse as main transcript	c.118-1043G>T		intron_variant		5		ENSP00000428268	P4	O60610-3
DIAPH1	ENST00000523100.5 linkuse as main transcript	c.128G>T	p.Arg43Leu	missense_variant, NMD_transcript_variant	2/11	5		ENSP00000428208

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

249056

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135112

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:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460230

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726524

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;.;T

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.82

T;T;T

M_CAP

Uncertain

0.20

MetaRNN

Uncertain

0.53

D;D;D

MetaSVM

Benign

-0.38

MutationAssessor

Benign

1.5

L;.;.

MutationTaster

Benign

1.0

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

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-1.6

N;.;N

REVEL

Uncertain

0.50

Sift

Benign

0.049

D;.;D

Sift4G

Benign

0.14

T;.;T

Polyphen

1.0

D;.;.

Vest4

0.51

MutPred

0.32

Loss of MoRF binding (P = 0.0166);Loss of MoRF binding (P = 0.0166);Loss of MoRF binding (P = 0.0166);

MVP

0.93

MPC

0.93

ClinPred

0.83

GERP RS

5.2

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.31

gMVP

0.42

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