rs142090969

Variant names:

• chr2-131528195-C-G
• rs142090969
• NM_001258306.3:c.225C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-131528195-C-G
• chr2-131528195-C-A
• chr2-131528195-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001258306.3(CCDC74A):​c.225C>G​(p.Ile75Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000713 in 1,613,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000076 (0 hom.)
• Consequence: CCDC74A NM_001258306.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.195
• Publications: 1 publications found

Genes affected

CCDC74A (HGNC:25197): (coiled-coil domain containing 74A)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.052033395).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258306.3. 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
	CCDC74A	NM_001258306.3	MANE Select	c.225C>G	p.Ile75Met	missense	Exon 1 of 8	NP_001245235.1	Q96AQ1-2
	CCDC74A	NM_001349042.2		c.225C>G	p.Ile75Met	missense	Exon 1 of 8	NP_001335971.1
	CCDC74A	NM_138770.4		c.225C>G	p.Ile75Met	missense	Exon 1 of 8	NP_620125.1	Q96AQ1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC74A	ENST00000409856.8	TSL:1 MANE Select	c.225C>G	p.Ile75Met	missense	Exon 1 of 8	ENSP00000387009.3	Q96AQ1-2
	CCDC74A	ENST00000295171.10	TSL:1	c.225C>G	p.Ile75Met	missense	Exon 1 of 8	ENSP00000295171.6	Q96AQ1-1
	CCDC74A	ENST00000467992.6	TSL:1	c.225C>G	p.Ile75Met	missense	Exon 1 of 7	ENSP00000444610.2	F5GZA4

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152132 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000174 AC: 43 AN: 246552 AF XY: 0.000179

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00180

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000182

Gnomad OTH exome AF: 0.000662

GnomAD4 exome AF: 0.0000760 AC: 111 AN: 1461130 Hom.: 0 Cov.: 32 AF XY: 0.0000894 AC XY: 65 AN XY: 726842

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00142 AC: 37 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.000522 AC: 45 AN: 86166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53262

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000189 AC: 21 AN: 1111688

Other (OTH) AF: 0.000133 AC: 8 AN: 60334

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152248 Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3 AN XY: 74428

African (AFR) AF: 0.00 AC: 0 AN: 41556

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000217 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.000198 AC: 24

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	Uncertain	0.39
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.045	T
Eigen	Benign	0.11
Eigen_PC	Benign	-0.052
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.84	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.20
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.18
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.99	D
Vest4		0.49
MutPred		0.25		Loss of catalytic residue at I75 (P = 0.0745)
MVP		0.37
MPC		2.5
ClinPred		0.17	T
GERP RS		0.54
PromoterAI		-0.063	Neutral
Varity_R		0.50
gMVP		0.43
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs142090969; hg19: chr2-132285768;