Genetic Variant DNAH12:p.Leu3213Leu (chr3-57352120-C-G) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001366028.2(DNAH12):c.9639G>C(p.Leu3213Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,527,738 control chromosomes in the GnomAD database, including 45,039 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4503 hom., cov: 32)

Exomes 𝑓: 0.23 ( 40536 hom. )

Consequence

DNAH12
NM_001366028.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.183

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 3-57352120-C-G is Benign according to our data. Variant chr3-57352120-C-G is described in ClinVar as [Benign]. Clinvar id is 402631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.183 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH12	NM_001366028.2 link	c.9639G>C	p.Leu3213Leu	synonymous_variant	Exon 60 of 74	ENST00000495027.6	NP_001352957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH12	ENST00000495027.6 link	c.9639G>C	p.Leu3213Leu	synonymous_variant	Exon 60 of 74	5	NM_001366028.2	ENSP00000418137.2	E9PG32
DNAH12	ENST00000351747.6 link	c.7035G>C	p.Leu2345Leu	synonymous_variant	Exon 45 of 59	5		ENSP00000295937.3	Q6ZR08-1
DNAH12	ENST00000466540.2 link	c.114G>C	p.Leu38Leu	synonymous_variant	Exon 2 of 15	5		ENSP00000420359.2	H7C5N3

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34195

AN:

151848

Hom.:

4501

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.351

Gnomad AMR

AF:

0.310

Gnomad ASJ

AF:

0.334

Gnomad EAS

AF:

0.401

Gnomad SAS

AF:

0.401

Gnomad FIN

AF:

0.301

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.226

Gnomad OTH

AF:

0.230

GnomAD3 exomes

AF:

0.278

AC:

38176

AN:

137390

Hom.:

5786

AF XY:

0.282

AC XY:

20507

AN XY:

72688

show subpopulations

Gnomad AFR exome

AF:

0.116

Gnomad AMR exome

AF:

0.326

Gnomad ASJ exome

AF:

0.340

Gnomad EAS exome

AF:

0.381

Gnomad SAS exome

AF:

0.369

Gnomad FIN exome

AF:

0.299

Gnomad NFE exome

AF:

0.222

Gnomad OTH exome

AF:

0.262

GnomAD4 exome

AF:

0.233

AC:

321213

AN:

1375770

Hom.:

40536

Cov.:

AF XY:

0.238

AC XY:

161343

AN XY:

677544

show subpopulations

Gnomad4 AFR exome

AF:

0.117

Gnomad4 AMR exome

AF:

0.323

Gnomad4 ASJ exome

AF:

0.341

Gnomad4 EAS exome

AF:

0.420

Gnomad4 SAS exome

AF:

0.375

Gnomad4 FIN exome

AF:

0.298

Gnomad4 NFE exome

AF:

0.212

Gnomad4 OTH exome

AF:

0.250

GnomAD4 genome

AF:

0.225

AC:

34207

AN:

151968

Hom.:

4503

Cov.:

AF XY:

0.235

AC XY:

17485

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.119

Gnomad4 AMR

AF:

0.309

Gnomad4 ASJ

AF:

0.334

Gnomad4 EAS

AF:

0.401

Gnomad4 SAS

AF:

0.402

Gnomad4 FIN

AF:

0.301

Gnomad4 NFE

AF:

0.226

Gnomad4 OTH

AF:

0.235

Alfa

AF:

0.236

Hom.:

1477

Bravo

AF:

0.216

Asia WGS

AF:

0.427

AC:

1476

AN:

3462

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

-0.37

CADD

Benign

1.2

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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