Variant rs6768943 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.4338C>T(p.Tyr1446Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 1,550,476 control chromosomes in the GnomAD database, including 210,621 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 16936 hom., cov: 32)

Exomes 𝑓: 0.52 ( 193685 hom. )

Consequence

DNAH12
NM_001366028.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.378

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=-0.51).

BP6

Variant 3-57445261-G-A is Benign according to our data. Variant chr3-57445261-G-A is described in ClinVar as [Benign]. Clinvar id is 402637.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.378 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.574 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.4338C>T	p.Tyr1446Tyr	synonymous_variant	28/74	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.4338C>T	p.Tyr1446Tyr	synonymous_variant	28/74	5	NM_001366028.2	ENSP00000418137.2		E9PG32
DNAH12	ENST00000351747.6 linkuse as main transcript	c.4269C>T	p.Tyr1423Tyr	synonymous_variant	28/59	5		ENSP00000295937.3		Q6ZR08-1

Frequencies

GnomAD3 genomes

AF:

0.446

AC:

67692

AN:

151898

Hom.:

16938

Cov.:

show subpopulations

Gnomad AFR

AF:

0.200

Gnomad AMI

AF:

0.626

Gnomad AMR

AF:

0.515

Gnomad ASJ

AF:

0.630

Gnomad EAS

AF:

0.419

Gnomad SAS

AF:

0.591

Gnomad FIN

AF:

0.605

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.533

Gnomad OTH

AF:

0.491

GnomAD3 exomes

AF:

0.522

AC:

81365

AN:

155998

Hom.:

22159

AF XY:

0.531

AC XY:

43875

AN XY:

82686

show subpopulations

Gnomad AFR exome

AF:

0.185

Gnomad AMR exome

AF:

0.492

Gnomad ASJ exome

AF:

0.635

Gnomad EAS exome

AF:

0.410

Gnomad SAS exome

AF:

0.586

Gnomad FIN exome

AF:

0.600

Gnomad NFE exome

AF:

0.534

Gnomad OTH exome

AF:

0.535

GnomAD4 exome

AF:

0.522

AC:

730033

AN:

1398460

Hom.:

193685

Cov.:

AF XY:

0.526

AC XY:

362467

AN XY:

689642

show subpopulations

Gnomad4 AFR exome

AF:

0.187

Gnomad4 AMR exome

AF:

0.497

Gnomad4 ASJ exome

AF:

0.634

Gnomad4 EAS exome

AF:

0.443

Gnomad4 SAS exome

AF:

0.586

Gnomad4 FIN exome

AF:

0.596

Gnomad4 NFE exome

AF:

0.524

Gnomad4 OTH exome

AF:

0.519

GnomAD4 genome

AF:

0.445

AC:

67694

AN:

152016

Hom.:

16936

Cov.:

AF XY:

0.453

AC XY:

33642

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.200

Gnomad4 AMR

AF:

0.514

Gnomad4 ASJ

AF:

0.630

Gnomad4 EAS

AF:

0.418

Gnomad4 SAS

AF:

0.592

Gnomad4 FIN

AF:

0.605

Gnomad4 NFE

AF:

0.533

Gnomad4 OTH

AF:

0.492

Alfa

AF:

0.501

Hom.:

10964

Bravo

AF:

0.423

Asia WGS

AF:

0.523

AC:

1819

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

-0.51

CADD

Benign

8.9

DANN

Benign

0.40

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

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