rs147307685

Variant names:

• chr2-131529653-A-C
• rs147307685
• NM_001258306.3:c.257A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-131529653-A-C
• chr2-131529653-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001258306.3(CCDC74A):​c.257A>C​(p.His86Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H86R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC74A NM_001258306.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25992334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC74A	NM_001258306.3	c.257A>C	p.His86Pro	missense_variant	Exon 2 of 8	ENST00000409856.8	NP_001245235.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC74A	ENST00000409856.8	c.257A>C	p.His86Pro	missense_variant	Exon 2 of 8	1	NM_001258306.3	ENSP00000387009.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000165 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Benign	0.83
DEOGEN2	Benign	0.032	T;T;.;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.79	T;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.3	M;.;M;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-4.5	D;.;D;D
REVEL	Benign	0.22
Sift	Uncertain	0.0080	D;.;D;D
Sift4G	Uncertain	0.0090	D;D;D;D
Polyphen		0.98	D;.;D;.
Vest4		0.42
MutPred		0.25		Gain of loop (P = 0.0121);Gain of loop (P = 0.0121);Gain of loop (P = 0.0121);.;
MVP		0.44
MPC		2.6
ClinPred		0.45	T
GERP RS		1.7
Varity_R		0.56
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs147307685; hg19: chr2-132287226;