NM_014460.4:c.115G>A

Variant names:

• chr22-41572080-G-A
• rs1329171666
• NM_014460.4:c.115G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_014460.4(CSDC2):​c.115G>A​(p.Gly39Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CSDC2 NM_014460.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.304
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.030517787).
• BP6: Variant 22-41572080-G-A is Benign according to our data. Variant chr22-41572080-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3077954.Status of the report is criteria_provided_single_submitter, 1 stars.

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.115G>A	p.Gly39Ser	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.115G>A	p.Gly39Ser	missense	Exon 2 of 4	ENSP00000302485.7	Q9Y534
	CSDC2	ENST00000901851.1		c.115G>A	p.Gly39Ser	missense	Exon 3 of 5	ENSP00000571910.1
	CSDC2	ENST00000901852.1		c.115G>A	p.Gly39Ser	missense	Exon 2 of 4	ENSP00000571911.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1209884 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 583516

African (AFR) AF: 0.00 AC: 0 AN: 25172

American (AMR) AF: 0.00 AC: 0 AN: 12000

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16312

East Asian (EAS) AF: 0.00 AC: 0 AN: 29640

South Asian (SAS) AF: 0.00 AC: 0 AN: 43250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4840

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 985272

Other (OTH) AF: 0.00 AC: 0 AN: 49028

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.068
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.0
DANN	Benign	0.89
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.30
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.69	N
REVEL	Benign	0.017
Sift	Benign	0.79	T
Sift4G	Benign	0.89	T
Polyphen		0.0	B
Vest4		0.069
MutPred		0.20		Gain of phosphorylation at G39 (P = 0.0078)
MVP		0.11
MPC		0.48
ClinPred		0.041	T
GERP RS		-5.7
PromoterAI		-0.015	Neutral
Varity_R		0.035
gMVP		0.21
Mutation Taster		=94/6	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: rs1329171666; hg19: chr22-41968084;