rs764264821

Variant names:

• chr15-92655467-T-A
• NM_207446.3:c.193A>T

Your query was ambiguous. Multiple possible variants found:

• chr15-92655467-T-A
• chr15-92655467-T-C
• chr15-92655467-T-G

Variant summary

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

The NM_207446.3(FAM174B):​c.193A>T​(p.Ser65Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,404,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict 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. S65G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: FAM174B NM_207446.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382

Genes affected

FAM174B (HGNC:34339): (family with sequence similarity 174 member B) Involved in Golgi organization. Located in Golgi apparatus and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.12914348).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM174B	NM_207446.3	c.193A>T	p.Ser65Cys	missense_variant	Exon 1 of 3	ENST00000327355.6	NP_997329.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM174B	ENST00000327355.6	c.193A>T	p.Ser65Cys	missense_variant	Exon 1 of 3	1	NM_207446.3	ENSP00000329040.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.12e-7 AC: 1 AN: 1404954 Hom.: 0 Cov.: 61 AF XY: 0.00000144 AC XY: 1 AN XY: 695292

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.20e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.26	T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.078
Sift	Benign	0.082	T
Sift4G	Benign	0.10	T
Polyphen		0.64	P
Vest4		0.11
MutPred		0.39		Loss of glycosylation at S65 (P = 4e-04);
MVP		0.10
MPC		0.36
ClinPred		0.24	T
GERP RS		2.0
Varity_R		0.089
gMVP		0.30

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-93198697;