3-57309679-T-C

Position:

• chr3-57309679-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001366028.2(DNAH12):​c.11072A>G​(p.Asp3691Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAH12 NM_001366028.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.82

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.315072).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH12	NM_001366028.2	c.11072A>G	p.Asp3691Gly	missense_variant	68/74	ENST00000495027.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH12	ENST00000495027.6	c.11072A>G	p.Asp3691Gly	missense_variant	68/74	5	NM_001366028.2	P1
DNAH12	ENST00000351747.6	c.8468A>G	p.Asp2823Gly	missense_variant	53/59	5
DNAH12	ENST00000466540.2	c.1412A>G	p.Asp471Gly	missense_variant	9/15	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 2023

The c.8468A>G (p.D2823G) alteration is located in exon 53 (coding exon 52) of the DNAH12 gene. This alteration results from a A to G substitution at nucleotide position 8468, causing the aspartic acid (D) at amino acid position 2823 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.047	T;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.89	N;N
PrimateAI	Uncertain	0.49	T
Polyphen		0.94	.;P
Vest4		0.29
MutPred		0.62		.;Gain of ubiquitination at K2827 (P = 0.1295);
MVP		0.57
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-57343707;