chr2-131528053-C-T

Variant names:

• chr2-131528053-C-T
• rs750083391
• NM_001258306.3:c.83C>T

Variant summary

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

The NM_001258306.3(CCDC74A):​c.83C>T​(p.Ser28Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,408,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: CCDC74A NM_001258306.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.28
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056728214).

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.83C>T	p.Ser28Phe	missense	Exon 1 of 8	NP_001245235.1	Q96AQ1-2
	CCDC74A	NM_001349042.2		c.83C>T	p.Ser28Phe	missense	Exon 1 of 8	NP_001335971.1
	CCDC74A	NM_138770.4		c.83C>T	p.Ser28Phe	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.83C>T	p.Ser28Phe	missense	Exon 1 of 8	ENSP00000387009.3	Q96AQ1-2
	CCDC74A	ENST00000295171.10	TSL:1	c.83C>T	p.Ser28Phe	missense	Exon 1 of 8	ENSP00000295171.6	Q96AQ1-1
	CCDC74A	ENST00000467992.6	TSL:1	c.83C>T	p.Ser28Phe	missense	Exon 1 of 7	ENSP00000444610.2	F5GZA4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000172 AC: 3 AN: 174882 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000215

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000497 AC: 7 AN: 1408804 Hom.: 0 Cov.: 32 AF XY: 0.00000143 AC XY: 1 AN XY: 698236

African (AFR) AF: 0.00 AC: 0 AN: 31170

American (AMR) AF: 0.00 AC: 0 AN: 31528

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23560

East Asian (EAS) AF: 0.000155 AC: 6 AN: 38794

South Asian (SAS) AF: 0.00 AC: 0 AN: 77502

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50204

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4560

European-Non Finnish (NFE) AF: 9.15e-7 AC: 1 AN: 1093474

Other (OTH) AF: 0.00 AC: 0 AN: 58012

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000333 AC: 4

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	0.21
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.090	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.3
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.033
Sift	Benign	0.030	D
Sift4G	Uncertain	0.022	D
Polyphen		0.27	B
Vest4		0.15
MutPred		0.26		Loss of phosphorylation at S28 (P = 0.003)
MVP		0.25
MPC		1.6
ClinPred		0.087	T
GERP RS		2.1
PromoterAI		-0.0018	Neutral
Varity_R		0.050
gMVP		0.16
Mutation Taster		=88/12	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: rs750083391; hg19: chr2-132285626;