rs190523466

Variant names:

• chr8-109280976-C-A
• rs190523466
• NM_032869.4:c.1020G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-109280976-C-A
• chr8-109280976-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032869.4(NUDCD1):​c.1020G>T​(p.Glu340Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000728 in 1,373,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: NUDCD1 NM_032869.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.931
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04960844).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032869.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDCD1	NM_032869.4	MANE Select	c.1020G>T	p.Glu340Asp	missense	Exon 6 of 10	NP_116258.2	Q96RS6-1
	NUDCD1	NM_001128211.2		c.933G>T	p.Glu311Asp	missense	Exon 6 of 10	NP_001121683.1	Q96RS6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDCD1	ENST00000239690.9	TSL:1 MANE Select	c.1020G>T	p.Glu340Asp	missense	Exon 6 of 10	ENSP00000239690.4	Q96RS6-1
	NUDCD1	ENST00000427660.6	TSL:1	c.933G>T	p.Glu311Asp	missense	Exon 6 of 10	ENSP00000410707.2	Q96RS6-2
	NUDCD1	ENST00000519607.5	TSL:1	n.*785G>T		non_coding_transcript_exon	Exon 7 of 11	ENSP00000430095.1	E5RGX7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000414 AC: 1 AN: 241730 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000917

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.28e-7 AC: 1 AN: 1373508 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 686240

African (AFR) AF: 0.00 AC: 0 AN: 31574

American (AMR) AF: 0.00 AC: 0 AN: 43316

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25126

East Asian (EAS) AF: 0.00 AC: 0 AN: 38894

South Asian (SAS) AF: 0.00 AC: 0 AN: 79162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51792

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5534

European-Non Finnish (NFE) AF: 9.61e-7 AC: 1 AN: 1041038

Other (OTH) AF: 0.00 AC: 0 AN: 57072

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	5.9
DANN	Benign	0.72
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.93
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.24
Sift	Benign	0.66	T
Sift4G	Benign	0.76	T
Polyphen		0.019	B
Vest4		0.14
MutPred		0.48		Gain of ubiquitination at K339 (P = 0.0817)
MVP		0.40
MPC		0.099
ClinPred		0.27	T
GERP RS		-0.10
Varity_R		0.054
gMVP		0.21
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs190523466; hg19: chr8-110293205;