3-57352120-C-A

Variant names:

• chr3-57352120-C-A
• rs12053975
• NM_001366028.2:c.9639G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4 BP7

The NM_001366028.2(DNAH12):​c.9639G>T​(p.Leu3213Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,377,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L3213L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: DNAH12 NM_001366028.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.189).
• BP7: Synonymous conserved (PhyloP=-0.183 with no splicing effect.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.26e-7 AC: 1 AN: 1377960 Hom.: 0 Cov.: 32 AF XY: 0.00000147 AC XY: 1 AN XY: 678578

African (AFR) AF: 0.00 AC: 0 AN: 30328

American (AMR) AF: 0.00 AC: 0 AN: 30680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24760

East Asian (EAS) AF: 0.00 AC: 0 AN: 34810

South Asian (SAS) AF: 0.00 AC: 0 AN: 72464

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49114

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5638

European-Non Finnish (NFE) AF: 9.32e-7 AC: 1 AN: 1072982

Other (OTH) AF: 0.00 AC: 0 AN: 57184

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	1.2
DANN	Benign	0.70
PhyloP100		-0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs12053975; hg19: chr3-57386148;