8-109281058-A-G

Variant names:

• chr8-109281058-A-G
• NM_032869.4:c.938T>C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_032869.4(NUDCD1):​c.938T>C​(p.Ile313Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUDCD1 NM_032869.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.71

Genes affected

NUDCD1 (HGNC:24306): (NudC domain containing 1) Predicted to be involved in immune system process. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.956

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUDCD1	NM_032869.4	c.938T>C	p.Ile313Thr	missense_variant	Exon 6 of 10	ENST00000239690.9	NP_116258.2
NUDCD1	NM_001128211.2	c.851T>C	p.Ile284Thr	missense_variant	Exon 6 of 10		NP_001121683.1
NUDCD1	XM_047422330.1	c.677T>C	p.Ile226Thr	missense_variant	Exon 6 of 10		XP_047278286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUDCD1	ENST00000239690.9	c.938T>C	p.Ile313Thr	missense_variant	Exon 6 of 10	1	NM_032869.4	ENSP00000239690.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 03, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.938T>C (p.I313T) alteration is located in exon 6 (coding exon 6) of the NUDCD1 gene. This alteration results from a T to C substitution at nucleotide position 938, causing the isoleucine (I) at amino acid position 313 to be replaced by a threonine (T). 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	0.17
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.025	D
MetaRNN	Pathogenic	0.96	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.52	P;B
Vest4		0.74
MutPred		0.84		Loss of stability (P = 0.026);.;
MVP		0.37
MPC		0.23
ClinPred		0.98	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.33
gMVP		0.61

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: chr8-110293287;