5-141573841-G-C

Variant names:

• chr5-141573841-G-C
• NM_005219.5:c.2009C>G

Variant summary

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

The NM_005219.5(DIAPH1):​c.2009C>G​(p.Pro670Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000145 in 1,375,690 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: 25)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: DIAPH1 NM_005219.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.50

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]

ACMG classification

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 rank	MANE	Protein	UniProt
DIAPH1	NM_005219.5	c.2009C>G	p.Pro670Arg	missense_variant	Exon 16 of 28	ENST00000389054.8	NP_005210.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIAPH1	ENST00000389054.8	c.2009C>G	p.Pro670Arg	missense_variant	Exon 16 of 28	5	NM_005219.5	ENSP00000373706.4
DIAPH1	ENST00000518047.5	c.1982C>G	p.Pro661Arg	missense_variant	Exon 15 of 27	5		ENSP00000428268.2
DIAPH1	ENST00000647433.1	c.2009C>G	p.Pro670Arg	missense_variant	Exon 16 of 29			ENSP00000494675.1
DIAPH1	ENST00000647330.1	n.*1236C>G		downstream_gene_variant				ENSP00000494308.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1375690 Hom.: 0 Cov.: 36 AF XY: 0.00000148 AC XY: 1 AN XY: 674018

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: 0.00000188

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T;.;T;.;T;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.36	T;T;T;T;T;T
M_CAP	Pathogenic	0.36	D
MetaRNN	Uncertain	0.58	D;D;D;D;D;D
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.1	M;.;.;.;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.6	N;.;.;N;N;N
REVEL	Uncertain	0.43
Sift	Uncertain	0.012	D;.;.;D;D;D
Sift4G	Benign	0.071	T;.;T;T;T;T
Polyphen		1.0	D;.;.;.;.;.
Vest4		0.46
MutPred		0.57		Gain of methylation at P670 (P = 0.0178);Gain of methylation at P670 (P = 0.0178);.;.;Gain of methylation at P670 (P = 0.0178);.;
MVP		0.87
MPC		0.12
ClinPred		0.89	D
GERP RS		4.3
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Varity_R		0.12
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-140953408;