chr3-57402387-T-C

Position:

• chr3-57402387-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
DNAH12	NM_001366028.2	c.6948+922A>G		intron_variant		ENST00000495027.6	NP_001352957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH12	ENST00000495027.6	c.6948+922A>G		intron_variant		5	NM_001366028.2	ENSP00000418137	P1
DNAH12	ENST00000351747.6	c.6929+5A>G		splice_donor_5th_base_variant, intron_variant		5		ENSP00000295937

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

Gnomad4 AFR exome AF: 0.234

Gnomad4 AMR exome AF: 0.488

Gnomad4 ASJ exome AF: 0.563

Gnomad4 EAS exome AF: 0.599

Gnomad4 SAS exome AF: 0.441

Gnomad4 FIN exome AF: 0.486

Gnomad4 NFE exome AF: 0.537

Gnomad4 OTH exome AF: 0.509

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

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.468

Alfa AF: 0.515 Hom.: 24084

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6445873; hg19: chr3-57388114;