18-34838101-C-G

Variant names:

• chr18-34838101-C-G
• rs768198248
• NM_001386795.1:c.1183C>G

Variant summary

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

The NM_001386795.1(DTNA):​c.1183C>G​(p.Pro395Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 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: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: DTNA NM_001386795.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.63

Genes affected

DTNA (HGNC:3057): (dystrobrevin alpha) The protein encoded by this gene belongs to the dystrobrevin subfamily of the dystrophin family. This protein is a component of the dystrophin-associated protein complex (DPC), which consists of dystrophin and several integral and peripheral membrane proteins, including dystroglycans, sarcoglycans, syntrophins and alpha- and beta-dystrobrevin. The DPC localizes to the sarcolemma and its disruption is associated with various forms of muscular dystrophy. Mutations in this gene are associated with left ventricular noncompaction with congenital heart defects. Multiple alternatively spliced transcript variants encoding different isoforms have been identified 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=0.1368393).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNA	NM_001386795.1	c.1183C>G	p.Pro395Ala	missense_variant	Exon 12 of 23	ENST00000444659.6	NP_001373724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNA	ENST00000444659.6	c.1183C>G	p.Pro395Ala	missense_variant	Exon 12 of 23	5	NM_001386795.1	ENSP00000405819.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74362

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.13	.;T;T;.;.
Eigen	Benign	-0.15
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D;.;T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.14	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	.;N;N;.;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.040	N;N;N;N;.
REVEL	Benign	0.060
Sift	Benign	0.52	T;T;T;D;.
Sift4G	Benign	0.75	T;T;T;T;T
Polyphen		0.0	B;B;B;.;B
Vest4		0.35
MutPred		0.20		.;Loss of catalytic residue at P367 (P = 0.0102);Loss of catalytic residue at P367 (P = 0.0102);.;.;
MVP		0.52
ClinPred		0.85	D
GERP RS		5.9
Varity_R		0.053

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

Other links and lift over

dbSNP: rs768198248; hg19: chr18-32418065;