chr10-80338513-G-A

Position:

• chr10-80338513-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001269053.2(DYDC1):​c.458C>T​(p.Pro153Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DYDC1 NM_001269053.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.48

Genes affected

DYDC1 (HGNC:23460): (DPY30 domain containing 1) This gene encodes a member of a family of proteins that contains a DPY30 domain. The encoded protein is involved in acrosome formation during spermatid development. This gene locus overlaps with a closely related gene on the opposite strand. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYDC1	NM_001269053.2	c.458C>T	p.Pro153Leu	missense_variant	6/7	ENST00000372202.6	NP_001255982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYDC1	ENST00000372202.6	c.458C>T	p.Pro153Leu	missense_variant	6/7	3	NM_001269053.2	ENSP00000361276.1
DYDC1	ENST00000372204.7	c.458C>T	p.Pro153Leu	missense_variant	7/8	1		ENSP00000361278.3
DYDC1	ENST00000421924.6	c.458C>T	p.Pro153Leu	missense_variant	5/6	1		ENSP00000402890.3
DYDC1	ENST00000454362.5	c.458C>T	p.???153???	splice_region_variant, synonymous_variant	6/6	2		ENSP00000414798.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Jan 03, 2024

The c.458C>T (p.P153L) alteration is located in exon 7 (coding exon 5) of the DYDC1 gene. This alteration results from a C to T substitution at nucleotide position 458, causing the proline (P) at amino acid position 153 to be replaced by a leucine (L). 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	Pathogenic	0.80
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;T;T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.86	.;D;.
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Uncertain	2.6	M;M;M
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-5.0	D;D;D
REVEL	Benign	0.27
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.64
MutPred		0.36		Loss of disorder (P = 0.0334);Loss of disorder (P = 0.0334);Loss of disorder (P = 0.0334);
MVP		0.43
MPC		0.50
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.56
gMVP		0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-82098269;