chr3-57402387-T-C

Variant names:

• chr3-57402387-T-C
• rs6445873
• NM_001366028.2:c.6948+922A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366028.2(DNAH12):​c.6948+922A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 1,304,226 control chromosomes in the GnomAD database, including 175,271 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.44 (15938 hom., cov: 30)
  • Exomes 𝑓: 0.52 (159333 hom.)
• Consequence: DNAH12 NM_001366028.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH12	NM_001366028.2	c.6948+922A>G		intron_variant	Intron 43 of 73	ENST00000495027.6	NP_001352957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH12	ENST00000495027.6	c.6948+922A>G		intron_variant	Intron 43 of 73	5	NM_001366028.2	ENSP00000418137.2
DNAH12	ENST00000351747.6	c.6929+5A>G		splice_region_variant, intron_variant	Intron 44 of 58	5		ENSP00000295937.3

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66793 AN: 151752 Hom.: 15933 Cov.: 30

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.469

GnomAD4 exome AF: 0.522 AC: 601596 AN: 1152358 Hom.: 159333 Cov.: 33 AF XY: 0.521 AC XY: 294226 AN XY: 565074

African (AFR) AF: 0.234 AC: 5697 AN: 24386

American (AMR) AF: 0.488 AC: 13788 AN: 28232

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 8967 AN: 15932

East Asian (EAS) AF: 0.599 AC: 7694 AN: 12840

South Asian (SAS) AF: 0.441 AC: 33572 AN: 76140

European-Finnish (FIN) AF: 0.486 AC: 13829 AN: 28430

Middle Eastern (MID) AF: 0.528 AC: 2322 AN: 4400

European-Non Finnish (NFE) AF: 0.537 AC: 494565 AN: 920398

Other (OTH) AF: 0.509 AC: 21162 AN: 41600

GnomAD4 genome AF: 0.440 AC: 66825 AN: 151868 Hom.: 15938 Cov.: 30 AF XY: 0.437 AC XY: 32436 AN XY: 74194

African (AFR) AF: 0.244 AC: 10102 AN: 41434

American (AMR) AF: 0.445 AC: 6785 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1993 AN: 3466

East Asian (EAS) AF: 0.592 AC: 3053 AN: 5156

South Asian (SAS) AF: 0.421 AC: 2021 AN: 4800

European-Finnish (FIN) AF: 0.483 AC: 5076 AN: 10510

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36162 AN: 67942

Other (OTH) AF: 0.468 AC: 984 AN: 2104

Alfa AF: 0.493 Hom.: 32945

Bravo AF: 0.435

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.3
PhyloP100		-0.015

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6445873; hg19: chr3-57388114;