4-99652808-C-A

Variant names:

• chr4-99652808-C-A
• rs1022953317
• NM_001354435.2:c.1841G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001354435.2(C4orf54):​c.1841G>T​(p.Ser614Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000013 in 1,536,012 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: C4orf54 NM_001354435.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.54

Genes affected

C4orf54 (HGNC:27741): (chromosome 4 open reading frame 54)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 4-99652808-C-A is Benign according to our data. Variant chr4-99652808-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2498956.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C4orf54	NM_001354435.2	c.1841G>T	p.Ser614Ile	missense_variant	Exon 2 of 3	ENST00000511828.2	NP_001341364.1
C4orf54	XM_373030.12	c.1940G>T	p.Ser647Ile	missense_variant	Exon 2 of 3		XP_373030.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C4orf54	ENST00000511828.2	c.1841G>T	p.Ser614Ile	missense_variant	Exon 2 of 3	1	NM_001354435.2	ENSP00000427555.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383824 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 682856

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152188 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74346

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

C4orf54: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-1.0	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.29
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Vest4		0.76
MutPred		0.38		Gain of sheet (P = 0.0011);
MVP		0.48
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.66
gMVP		0.73

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: rs1022953317; hg19: chr4-100573965;