5-141573692-G-C

Variant names:

• chr5-141573692-G-C
• NM_005219.5:c.2158C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005219.5(DIAPH1):​c.2158C>G​(p.Leu720Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DIAPH1 NM_005219.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.972

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2575119).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIAPH1	NM_005219.5	c.2158C>G	p.Leu720Val	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.2158C>G	p.Leu720Val	missense_variant	Exon 16 of 28	5	NM_005219.5	ENSP00000373706.4
DIAPH1	ENST00000518047.5	c.2131C>G	p.Leu711Val	missense_variant	Exon 15 of 27	5		ENSP00000428268.2
DIAPH1	ENST00000647433.1	c.2158C>G	p.Leu720Val	missense_variant	Exon 16 of 29			ENSP00000494675.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451106 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 720510

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: 9.05e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;.;T;.;T;.
Eigen	Benign	0.035
Eigen_PC	Benign	-0.026
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.82	T;T;T;T;T;T
M_CAP	Uncertain	0.090	D
MetaRNN	Benign	0.26	T;T;T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.6	L;.;.;.;.;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.1	N;.;.;N;N;N
REVEL	Benign	0.24
Sift	Benign	0.27	T;.;.;T;T;T
Sift4G	Benign	0.095	T;.;T;T;T;T
Polyphen		0.80	P;.;.;.;.;.
Vest4		0.46
MutPred		0.67		Loss of glycosylation at P719 (P = 0.1101);Loss of glycosylation at P719 (P = 0.1101);.;.;Loss of glycosylation at P719 (P = 0.1101);.;
MVP		0.73
MPC		0.12
ClinPred		0.36	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.074
gMVP		0.042

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: chr5-140953259;