rs200839105

Variant names:

• chr13-60016071-A-C
• rs200839105
• NM_001042517.2:c.701T>G

Your query was ambiguous. Multiple possible variants found:

• chr13-60016071-A-C
• chr13-60016071-A-G

Variant summary

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

The NM_001042517.2(DIAPH3):​c.701T>G​(p.Ile234Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I234T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DIAPH3 NM_001042517.2 missense, splice_region
• Scores: Splicing: ADA: 0.00009719
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990

Genes affected

DIAPH3 (HGNC:15480): (diaphanous related formin 3) This gene encodes a member of the diaphanous subfamily of the formin family. Members of this family are involved in actin remodeling and regulate cell movement and adhesion. Mutations in this gene are associated with autosomal dominant auditory neuropathy 1. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

DIAPH3-AS1 (HGNC:39915): (DIAPH3 antisense RNA 1)

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=0.14142746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIAPH3	NM_001042517.2	c.701T>G	p.Ile234Ser	missense_variant, splice_region_variant	Exon 6 of 28	ENST00000400324.9	NP_001035982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIAPH3	ENST00000400324.9	c.701T>G	p.Ile234Ser	missense_variant, splice_region_variant	Exon 6 of 28	1	NM_001042517.2	ENSP00000383178.3
DIAPH3	ENST00000400319.5	c.491T>G	p.Ile164Ser	missense_variant, splice_region_variant	Exon 4 of 26	1		ENSP00000383173.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000403 AC: 1 AN: 248064 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134630

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: 0.00000890

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	13
DANN	Benign	0.79
DEOGEN2	Benign	0.12	T;.;.;.;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.64	T;T;T;T;T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.14	T;T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.90	L;.;.;.;L
PrimateAI	Benign	0.40	T
PROVEAN	Benign	1.0	N;N;N;N;N
REVEL	Benign	0.22
Sift	Benign	0.49	T;T;T;T;T
Sift4G	Benign	0.40	T;T;T;T;T
Polyphen		0.0010	B;.;.;.;.
Vest4		0.22
MutPred		0.66		Gain of disorder (P = 0.0017);.;.;.;Gain of disorder (P = 0.0017);
MVP		0.82
MPC		0.19
ClinPred		0.26	T
GERP RS		0.55
Varity_R		0.073
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000097
dbscSNV1_RF	Benign	0.13
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

Other links and lift over

dbSNP: rs200839105; hg19: chr13-60590205;