Genetic Variant DNAH12:c.3053+9A>G (chr3-57458090-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001366028.2(DNAH12):c.3053+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 1,540,652 control chromosomes in the GnomAD database, including 352,759 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 34267 hom., cov: 32)

Exomes 𝑓: 0.68 ( 318492 hom. )

Consequence

DNAH12
NM_001366028.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.320

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=-0.88).

BP6

Variant 3-57458090-T-C is Benign according to our data. Variant chr3-57458090-T-C is described in ClinVar as [Benign]. Clinvar id is 402639.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH12	NM_001366028.2 link	c.3053+9A>G		intron_variant	Intron 21 of 73	ENST00000495027.6	NP_001352957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH12	ENST00000495027.6 link	c.3053+9A>G		intron_variant	Intron 21 of 73	5	NM_001366028.2	ENSP00000418137.2		E9PG32
DNAH12	ENST00000351747.6 link	c.2984+9A>G		intron_variant	Intron 21 of 58	5		ENSP00000295937.3		Q6ZR08-1

Frequencies

GnomAD3 genomes

AF:

0.669

AC:

101660

AN:

151900

Hom.:

34260

Cov.:

show subpopulations

Gnomad AFR

AF:

0.644

Gnomad AMI

AF:

0.831

Gnomad AMR

AF:

0.638

Gnomad ASJ

AF:

0.790

Gnomad EAS

AF:

0.489

Gnomad SAS

AF:

0.749

Gnomad FIN

AF:

0.724

Gnomad MID

AF:

0.703

Gnomad NFE

AF:

0.683

Gnomad OTH

AF:

0.677

GnomAD3 exomes

AF:

0.675

AC:

97787

AN:

144846

Hom.:

33618

AF XY:

0.683

AC XY:

52418

AN XY:

76728

show subpopulations

Gnomad AFR exome

AF:

0.639

Gnomad AMR exome

AF:

0.599

Gnomad ASJ exome

AF:

0.796

Gnomad EAS exome

AF:

0.473

Gnomad SAS exome

AF:

0.767

Gnomad FIN exome

AF:

0.731

Gnomad NFE exome

AF:

0.681

Gnomad OTH exome

AF:

0.676

GnomAD4 exome

AF:

0.676

AC:

938384

AN:

1388634

Hom.:

318492

Cov.:

AF XY:

0.679

AC XY:

464598

AN XY:

684398

show subpopulations

Gnomad4 AFR exome

AF:

0.643

Gnomad4 AMR exome

AF:

0.606

Gnomad4 ASJ exome

AF:

0.796

Gnomad4 EAS exome

AF:

0.520

Gnomad4 SAS exome

AF:

0.758

Gnomad4 FIN exome

AF:

0.720

Gnomad4 NFE exome

AF:

0.673

Gnomad4 OTH exome

AF:

0.679

GnomAD4 genome

AF:

0.669

AC:

101714

AN:

152018

Hom.:

34267

Cov.:

AF XY:

0.672

AC XY:

49947

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.644

Gnomad4 AMR

AF:

0.638

Gnomad4 ASJ

AF:

0.790

Gnomad4 EAS

AF:

0.489

Gnomad4 SAS

AF:

0.749

Gnomad4 FIN

AF:

0.724

Gnomad4 NFE

AF:

0.683

Gnomad4 OTH

AF:

0.675

Alfa

AF:

0.683

Hom.:

82481

Bravo

AF:

0.657

Asia WGS

AF:

0.656

AC:

2284

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

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.9

DANN

Benign

0.45

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