NM_014460.4:c.127C>T

Variant names:

• chr22-41572092-C-T
• rs372792554
• NM_014460.4:c.127C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014460.4(CSDC2):​c.127C>T​(p.Arg43Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000368 in 1,358,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R43Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000033 (0 hom.)
• Consequence: CSDC2 NM_014460.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.620
• Publications: 1 publications found

Genes affected

CSDC2 (HGNC:30359): (cold shock domain containing C2) Predicted to enable mRNA 3'-UTR binding activity. Predicted to be involved in regulation of mRNA stability. Predicted to be located in nucleus. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3745737).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014460.4. 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
	CSDC2	NM_014460.4	MANE Select	c.127C>T	p.Arg43Trp	missense	Exon 2 of 4	NP_055275.1	Q9Y534

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSDC2	ENST00000306149.12	TSL:1 MANE Select	c.127C>T	p.Arg43Trp	missense	Exon 2 of 4	ENSP00000302485.7	Q9Y534
	CSDC2	ENST00000901851.1		c.127C>T	p.Arg43Trp	missense	Exon 3 of 5	ENSP00000571910.1
	CSDC2	ENST00000901852.1		c.127C>T	p.Arg43Trp	missense	Exon 2 of 4	ENSP00000571911.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152082 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000332 AC: 4 AN: 1206354 Hom.: 0 Cov.: 32 AF XY: 0.00000172 AC XY: 1 AN XY: 581448

African (AFR) AF: 0.00 AC: 0 AN: 25170

American (AMR) AF: 0.00 AC: 0 AN: 12822

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16202

East Asian (EAS) AF: 0.00 AC: 0 AN: 29788

South Asian (SAS) AF: 0.00 AC: 0 AN: 41612

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4808

European-Non Finnish (NFE) AF: 0.00000407 AC: 4 AN: 983070

Other (OTH) AF: 0.00 AC: 0 AN: 48688

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152082 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74268

African (AFR) AF: 0.00 AC: 0 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67980

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.59	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.62
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.16
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.99	D
Vest4		0.53
MVP		0.50
MPC		0.96
ClinPred		0.94	D
GERP RS		2.7
PromoterAI		-0.017	Neutral
Varity_R		0.10
gMVP		0.39
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs372792554; hg19: chr22-41968096;