Variant 3-57470644-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001366028.2(DNAH12):c.1912-8A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 1,516,742 control chromosomes in the GnomAD database, including 348,272 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 34257 hom., cov: 32)

Exomes 𝑓: 0.68 ( 314015 hom. )

Consequence

DNAH12
NM_001366028.2 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002040

Clinical Significance

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

Conservation

PhyloP100: -0.410

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 3-57470644-T-C is Benign according to our data. Variant chr3-57470644-T-C is described in ClinVar as [Benign]. Clinvar id is 402640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.732 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.1912-8A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000495027.6	NP_001352957.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
DNAH12	ENST00000495027.6 linkuse as main transcript	c.1912-8A>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5	NM_001366028.2	ENSP00000418137	P1
DNAH12	ENST00000351747.6 linkuse as main transcript	c.1912-8A>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5		ENSP00000295937		Q6ZR08-1
DNAH12	ENST00000389536.8 linkuse as main transcript	c.1912-8A>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5		ENSP00000374187

Frequencies

GnomAD3 genomes

AF:

0.669

AC:

101637

AN:

151954

Hom.:

34249

Cov.:

show subpopulations

Gnomad AFR

AF:

0.641

Gnomad AMI

AF:

0.832

Gnomad AMR

AF:

0.638

Gnomad ASJ

AF:

0.790

Gnomad EAS

AF:

0.489

Gnomad SAS

AF:

0.752

Gnomad FIN

AF:

0.724

Gnomad MID

AF:

0.703

Gnomad NFE

AF:

0.683

Gnomad OTH

AF:

0.675

GnomAD3 exomes

AF:

0.683

AC:

85726

AN:

125600

Hom.:

29704

AF XY:

0.687

AC XY:

46064

AN XY:

67004

show subpopulations

Gnomad AFR exome

AF:

0.637

Gnomad AMR exome

AF:

0.615

Gnomad ASJ exome

AF:

0.798

Gnomad EAS exome

AF:

0.478

Gnomad SAS exome

AF:

0.767

Gnomad FIN exome

AF:

0.728

Gnomad NFE exome

AF:

0.684

Gnomad OTH exome

AF:

0.680

GnomAD4 exome

AF:

0.677

AC:

923708

AN:

1364670

Hom.:

314015

Cov.:

AF XY:

0.680

AC XY:

457136

AN XY:

672722

show subpopulations

Gnomad4 AFR exome

AF:

0.641

Gnomad4 AMR exome

AF:

0.615

Gnomad4 ASJ exome

AF:

0.796

Gnomad4 EAS exome

AF:

0.519

Gnomad4 SAS exome

AF:

0.759

Gnomad4 FIN exome

AF:

0.721

Gnomad4 NFE exome

AF:

0.674

Gnomad4 OTH exome

AF:

0.680

GnomAD4 genome

AF:

0.669

AC:

101692

AN:

152072

Hom.:

34257

Cov.:

AF XY:

0.672

AC XY:

49939

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.641

Gnomad4 AMR

AF:

0.637

Gnomad4 ASJ

AF:

0.790

Gnomad4 EAS

AF:

0.489

Gnomad4 SAS

AF:

0.753

Gnomad4 FIN

AF:

0.724

Gnomad4 NFE

AF:

0.683

Gnomad4 OTH

AF:

0.674

Alfa

AF:

0.688

Hom.:

11503

Bravo

AF:

0.656

Asia WGS

AF:

0.657

AC:

2285

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

-0.83

CADD

Benign

7.5

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000020

dbscSNV1_RF

Benign

0.0

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