rs1447273780

Variant names:

• chr2-131528203-T-C
• rs1447273780
• NM_001258306.3:c.233T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-131528203-T-C
• chr2-131528203-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001258306.3(CCDC74A):​c.233T>C​(p.Leu78Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. L78R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCDC74A NM_001258306.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.89

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.773

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC74A	NM_001258306.3	c.233T>C	p.Leu78Pro	missense_variant	Exon 1 of 8	ENST00000409856.8	NP_001245235.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC74A	ENST00000409856.8	c.233T>C	p.Leu78Pro	missense_variant	Exon 1 of 8	1	NM_001258306.3	ENSP00000387009.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000407 AC: 1 AN: 245696 Hom.: 0 AF XY: 0.00000748 AC XY: 1 AN XY: 133640

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460718 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726614

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T;T;.
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.87	D;D;T
M_CAP	Pathogenic	0.32	D
MetaRNN	Pathogenic	0.77	D;D;D
MetaSVM	Uncertain	0.24	D
MutationAssessor	Pathogenic	3.0	M;.;M
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-6.2	D;.;D
REVEL	Pathogenic	0.70
Sift	Pathogenic	0.0	D;.;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.99	D;.;D
Vest4		0.70
MutPred		0.42		Loss of helix (P = 3e-04);Loss of helix (P = 3e-04);Loss of helix (P = 3e-04);
MVP		0.88
MPC		3.1
ClinPred		0.99	D
GERP RS		2.8
Varity_R		0.97
gMVP		0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs1447273780; hg19: chr2-132285776;