chr3-57409039-T-C

Variant names:

• chr3-57409039-T-C
• rs1916284
• NM_001366028.2:c.6021-504A>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.6021-504A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 152,056 control chromosomes in the GnomAD database, including 22,218 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 0.53 (22218 hom., cov: 32)
• Consequence: DNAH12 NM_001366028.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288
• Publications: 13 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH12	NM_001366028.2	c.6021-504A>G		intron_variant	Intron 39 of 73	ENST00000495027.6	NP_001352957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH12	ENST00000495027.6	c.6021-504A>G		intron_variant	Intron 39 of 73	5	NM_001366028.2	ENSP00000418137.2
DNAH12	ENST00000351747.6	c.5964-504A>G		intron_variant	Intron 39 of 58	5		ENSP00000295937.3

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79834 AN: 151938 Hom.: 22201 Cov.: 32

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.491

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.526 AC: 79907 AN: 152056 Hom.: 22218 Cov.: 32 AF XY: 0.529 AC XY: 39300 AN XY: 74318

African (AFR) AF: 0.714 AC: 29633 AN: 41474

American (AMR) AF: 0.516 AC: 7885 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1365 AN: 3470

East Asian (EAS) AF: 0.411 AC: 2122 AN: 5162

South Asian (SAS) AF: 0.556 AC: 2682 AN: 4820

European-Finnish (FIN) AF: 0.492 AC: 5204 AN: 10572

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29433 AN: 67956

Other (OTH) AF: 0.493 AC: 1040 AN: 2110

Alfa AF: 0.468 Hom.: 30150

Bravo AF: 0.529

Asia WGS AF: 0.538 AC: 1869 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.2
DANN	Benign	0.84
PhyloP100		0.29
Mutation Taster		=100/0	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: rs1916284; hg19: chr3-57394766;