Variant 3-57483370-C-T 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.1650+6G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 1,538,730 control chromosomes in the GnomAD database, including 351,652 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 ( 34175 hom., cov: 31)

Exomes 𝑓: 0.68 ( 317477 hom. )

Consequence

DNAH12
NM_001366028.2 splice_region, intron

Scores

Splicing: ADA: 0.00005776

Clinical Significance

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

Conservation

PhyloP100: 0.0260

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=-0.82).

BP6

Variant 3-57483370-C-T is Benign according to our data. Variant chr3-57483370-C-T is described in ClinVar as [Benign]. Clinvar id is 402641.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.733 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.1650+6G>A		splice_region_variant, intron_variant		ENST00000495027.6	NP_001352957.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
DNAH12	ENST00000495027.6 linkuse as main transcript	c.1650+6G>A	splice_region_variant, intron_variant	5	NM_001366028.2	ENSP00000418137.2	E9PG32
DNAH12	ENST00000351747.6 linkuse as main transcript	c.1650+6G>A	splice_region_variant, intron_variant	5		ENSP00000295937.3	Q6ZR08-1
DNAH12	ENST00000389536.8 linkuse as main transcript	c.1650+6G>A	splice_region_variant, intron_variant	5		ENSP00000374187.4	J3QTM1

Frequencies

GnomAD3 genomes

AF:

0.668

AC:

101510

AN:

151852

Hom.:

34167

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:

0.488

Gnomad SAS

AF:

0.753

Gnomad FIN

AF:

0.724

Gnomad MID

AF:

0.703

Gnomad NFE

AF:

0.683

Gnomad OTH

AF:

0.674

GnomAD3 exomes

AF:

0.670

AC:

97747

AN:

145998

Hom.:

33399

AF XY:

0.677

AC XY:

52139

AN XY:

76962

show subpopulations

Gnomad AFR exome

AF:

0.632

Gnomad AMR exome

AF:

0.583

Gnomad ASJ exome

AF:

0.790

Gnomad EAS exome

AF:

0.465

Gnomad SAS exome

AF:

0.760

Gnomad FIN exome

AF:

0.725

Gnomad NFE exome

AF:

0.678

Gnomad OTH exome

AF:

0.672

GnomAD4 exome

AF:

0.675

AC:

936096

AN:

1386760

Hom.:

317477

Cov.:

AF XY:

0.678

AC XY:

463593

AN XY:

683678

show subpopulations

Gnomad4 AFR exome

AF:

0.639

Gnomad4 AMR exome

AF:

0.593

Gnomad4 ASJ exome

AF:

0.794

Gnomad4 EAS exome

AF:

0.519

Gnomad4 SAS exome

AF:

0.758

Gnomad4 FIN exome

AF:

0.720

Gnomad4 NFE exome

AF:

0.672

Gnomad4 OTH exome

AF:

0.679

GnomAD4 genome

AF:

0.668

AC:

101565

AN:

151970

Hom.:

34175

Cov.:

AF XY:

0.672

AC XY:

49884

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.641

Gnomad4 AMR

AF:

0.637

Gnomad4 ASJ

AF:

0.790

Gnomad4 EAS

AF:

0.488

Gnomad4 SAS

AF:

0.753

Gnomad4 FIN

AF:

0.724

Gnomad4 NFE

AF:

0.683

Gnomad4 OTH

AF:

0.673

Alfa

AF:

0.682

Hom.:

27908

Bravo

AF:

0.656

Asia WGS

AF:

0.657

AC:

2286

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

-0.82

CADD

Benign

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000058

dbscSNV1_RF

Benign

0.0020

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