Variant 3-57446258-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001366028.2(DNAH12):c.3952C>T(p.Leu1318Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 1,550,246 control chromosomes in the GnomAD database, including 212,370 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 17154 hom., cov: 32)

Exomes 𝑓: 0.52 ( 195216 hom. )

Consequence

DNAH12
NM_001366028.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.16

Variant links:

Genes affected

DNAH12 (HGNC:2943): (dynein axonemal heavy chain 12) Predicted to enable several functions, including ATP binding activity; dynein intermediate chain binding activity; and dynein light intermediate chain binding activity. Predicted to be involved in microtubule-based movement. Predicted to be located in cilium; cytoplasm; and microtubule. Predicted to be part of dynein complex. [provided by Alliance of Genome Resources, Apr 2022]

DNAH12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 3-57446258-G-A is Benign according to our data. Variant chr3-57446258-G-A is described in ClinVar as [Benign]. Clinvar id is 402638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.16 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH12	NM_001366028.2 linkuse as main transcript	c.3952C>T	p.Leu1318Leu	synonymous_variant	27/74	ENST00000495027.6	NP_001352957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH12	ENST00000495027.6 linkuse as main transcript	c.3952C>T	p.Leu1318Leu	synonymous_variant	27/74	5	NM_001366028.2	ENSP00000418137.2		E9PG32
DNAH12	ENST00000351747.6 linkuse as main transcript	c.3883C>T	p.Leu1295Leu	synonymous_variant	27/59	5		ENSP00000295937.3		Q6ZR08-1

Frequencies

GnomAD3 genomes

AF:

0.450

AC:

68385

AN:

151868

Hom.:

17155

Cov.:

show subpopulations

Gnomad AFR

AF:

0.212

Gnomad AMI

AF:

0.629

Gnomad AMR

AF:

0.518

Gnomad ASJ

AF:

0.635

Gnomad EAS

AF:

0.421

Gnomad SAS

AF:

0.594

Gnomad FIN

AF:

0.606

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.535

Gnomad OTH

AF:

0.497

GnomAD3 exomes

AF:

0.525

AC:

82766

AN:

157752

Hom.:

22588

AF XY:

0.534

AC XY:

44459

AN XY:

83258

show subpopulations

Gnomad AFR exome

AF:

0.200

Gnomad AMR exome

AF:

0.496

Gnomad ASJ exome

AF:

0.640

Gnomad EAS exome

AF:

0.413

Gnomad SAS exome

AF:

0.590

Gnomad FIN exome

AF:

0.600

Gnomad NFE exome

AF:

0.537

Gnomad OTH exome

AF:

0.540

GnomAD4 exome

AF:

0.524

AC:

733151

AN:

1398260

Hom.:

195216

Cov.:

AF XY:

0.528

AC XY:

364059

AN XY:

689638

show subpopulations

Gnomad4 AFR exome

AF:

0.202

Gnomad4 AMR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.640

Gnomad4 EAS exome

AF:

0.443

Gnomad4 SAS exome

AF:

0.589

Gnomad4 FIN exome

AF:

0.597

Gnomad4 NFE exome

AF:

0.526

Gnomad4 OTH exome

AF:

0.524

GnomAD4 genome

AF:

0.450

AC:

68390

AN:

151986

Hom.:

17154

Cov.:

AF XY:

0.458

AC XY:

33999

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.211

Gnomad4 AMR

AF:

0.517

Gnomad4 ASJ

AF:

0.635

Gnomad4 EAS

AF:

0.421

Gnomad4 SAS

AF:

0.595

Gnomad4 FIN

AF:

0.606

Gnomad4 NFE

AF:

0.535

Gnomad4 OTH

AF:

0.498

Alfa

AF:

0.525

Hom.:

31892

Bravo

AF:

0.429

Asia WGS

AF:

0.527

AC:

1835

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

1.9

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over