rs6768943

Variant names:

• chr3-57445261-G-A
• rs6768943
• NM_001366028.2:c.4338C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-57445261-G-A
• chr3-57445261-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.378
• Publications: 14 publications found

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 Gene-Disease associations (from GenCC):

• oligoasthenoteratozoospermia

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
DNAH12	NM_001366028.2	c.4338C>T	p.Tyr1446Tyr	synonymous_variant	Exon 28 of 74	ENST00000495027.6	NP_001352957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH12	ENST00000495027.6	c.4338C>T	p.Tyr1446Tyr	synonymous_variant	Exon 28 of 74	5	NM_001366028.2	ENSP00000418137.2
DNAH12	ENST00000351747.6	c.4269C>T	p.Tyr1423Tyr	synonymous_variant	Exon 28 of 59	5		ENSP00000295937.3

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67692 AN: 151898 Hom.: 16938 Cov.: 32

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

GnomAD2 exomes AF: 0.522 AC: 81365 AN: 155998 AF XY: 0.531

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 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.: 47 AF XY: 0.526 AC XY: 362467 AN XY: 689642

African (AFR) AF: 0.187 AC: 5913 AN: 31582

American (AMR) AF: 0.497 AC: 17700 AN: 35588

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 15944 AN: 25166

East Asian (EAS) AF: 0.443 AC: 15800 AN: 35704

South Asian (SAS) AF: 0.586 AC: 46348 AN: 79066

European-Finnish (FIN) AF: 0.596 AC: 29364 AN: 49250

Middle Eastern (MID) AF: 0.600 AC: 3414 AN: 5690

European-Non Finnish (NFE) AF: 0.524 AC: 565444 AN: 1078450

Other (OTH) AF: 0.519 AC: 30106 AN: 57964

GnomAD4 genome AF: 0.445 AC: 67694 AN: 152016 Hom.: 16936 Cov.: 32 AF XY: 0.453 AC XY: 33642 AN XY: 74276

African (AFR) AF: 0.200 AC: 8290 AN: 41464

American (AMR) AF: 0.514 AC: 7846 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2184 AN: 3468

East Asian (EAS) AF: 0.418 AC: 2158 AN: 5158

South Asian (SAS) AF: 0.592 AC: 2856 AN: 4822

European-Finnish (FIN) AF: 0.605 AC: 6375 AN: 10536

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36226 AN: 67992

Other (OTH) AF: 0.492 AC: 1036 AN: 2104

Alfa AF: 0.496 Hom.: 14137

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

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	-0.51
CADD	Benign	8.9
DANN	Benign	0.40
PhyloP100		0.38
Mutation Taster		=71/29	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6768943; hg19: chr3-57430988; COSMIC: COSV61060182;