3-57458090-T-C

Variant names:

• chr3-57458090-T-C
• rs6768661
• NM_001366028.2:c.3053+9A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.320
• Publications: 10 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 -20 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 VariationId is 402639.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
DNAH12	NM_001366028.2	c.3053+9A>G		intron_variant	Intron 21 of 73	ENST00000495027.6	NP_001352957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH12	ENST00000495027.6	c.3053+9A>G		intron_variant	Intron 21 of 73	5	NM_001366028.2	ENSP00000418137.2
DNAH12	ENST00000351747.6	c.2984+9A>G		intron_variant	Intron 21 of 58	5		ENSP00000295937.3

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

GnomAD2 exomes AF: 0.675 AC: 97787 AN: 144846 AF XY: 0.683

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 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

African (AFR) AF: 0.643 AC: 19761 AN: 30720

American (AMR) AF: 0.606 AC: 19948 AN: 32924

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 19694 AN: 24748

East Asian (EAS) AF: 0.520 AC: 18538 AN: 35660

South Asian (SAS) AF: 0.758 AC: 58158 AN: 76718

European-Finnish (FIN) AF: 0.720 AC: 35384 AN: 49130

Middle Eastern (MID) AF: 0.748 AC: 4201 AN: 5620

European-Non Finnish (NFE) AF: 0.673 AC: 723661 AN: 1075648

Other (OTH) AF: 0.679 AC: 39039 AN: 57466

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

African (AFR) AF: 0.644 AC: 26680 AN: 41450

American (AMR) AF: 0.638 AC: 9741 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 2737 AN: 3466

East Asian (EAS) AF: 0.489 AC: 2527 AN: 5170

South Asian (SAS) AF: 0.749 AC: 3618 AN: 4828

European-Finnish (FIN) AF: 0.724 AC: 7629 AN: 10536

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.683 AC: 46392 AN: 67972

Other (OTH) AF: 0.675 AC: 1429 AN: 2116

Alfa AF: 0.678 Hom.: 155180

Bravo AF: 0.657

Asia WGS AF: 0.656 AC: 2284 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.9
DANN	Benign	0.45
PhyloP100		-0.32
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: rs6768661; hg19: chr3-57443817; COSMIC: COSV61056388;