3-57458090-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001366028.2(DNAH12):c.3053+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 1,540,652 control chromosomes in the GnomAD database, including 352,759 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.67 (34267 hom., cov: 32)
  • Exomes 𝑓: 0.68 (318492 hom.)
• Consequence: DNAH12 NM_001366028.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.320

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-57458090-T-C is Benign according to our data. Variant chr3-57458090-T-C is described in ClinVar as [Benign]. Clinvar id is 402639.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH12	NM_001366028.2	c.3053+9A>G		intron_variant		ENST00000495027.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH12	ENST00000495027.6	c.3053+9A>G		intron_variant		5	NM_001366028.2	P1
DNAH12	ENST00000351747.6	c.2984+9A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101660 AN: 151900 Hom.: 34260 Cov.: 32

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.831

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.677

GnomAD3 exomes AF: 0.675 AC: 97787 AN: 144846 Hom.: 33618 AF XY: 0.683 AC XY: 52418 AN XY: 76728

Gnomad AFR exome AF: 0.639

Gnomad AMR exome AF: 0.599

Gnomad ASJ exome AF: 0.796

Gnomad EAS exome AF: 0.473

Gnomad SAS exome AF: 0.767

Gnomad FIN exome AF: 0.731

Gnomad NFE exome AF: 0.681

Gnomad OTH exome AF: 0.676

GnomAD4 exome AF: 0.676 AC: 938384 AN: 1388634 Hom.: 318492 Cov.: 49 AF XY: 0.679 AC XY: 464598 AN XY: 684398

Gnomad4 AFR exome AF: 0.643

Gnomad4 AMR exome AF: 0.606

Gnomad4 ASJ exome AF: 0.796

Gnomad4 EAS exome AF: 0.520

Gnomad4 SAS exome AF: 0.758

Gnomad4 FIN exome AF: 0.720

Gnomad4 NFE exome AF: 0.673

Gnomad4 OTH exome AF: 0.679

GnomAD4 genome AF: 0.669 AC: 101714 AN: 152018 Hom.: 34267 Cov.: 32 AF XY: 0.672 AC XY: 49947 AN XY: 74304

Gnomad4 AFR AF: 0.644

Gnomad4 AMR AF: 0.638

Gnomad4 ASJ AF: 0.790

Gnomad4 EAS AF: 0.489

Gnomad4 SAS AF: 0.749

Gnomad4 FIN AF: 0.724

Gnomad4 NFE AF: 0.683

Gnomad4 OTH AF: 0.675

Alfa AF: 0.683 Hom.: 82481

Bravo AF: 0.657

Asia WGS AF: 0.656 AC: 2284 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.9
Dann	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs6768661; hg19: chr3-57443817; COSMIC: COSV61056388;