rs1447683740

Variant names:

• chr15-92630308-T-C
• rs1447683740
• NM_207446.3:c.382A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_207446.3(FAM174B):​c.382A>G​(p.Ile128Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,476 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: FAM174B NM_207446.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.28
• Publications: 0 publications found

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]

ENSG00000305093 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207446.3. 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
	FAM174B	NM_207446.3	MANE Select	c.382A>G	p.Ile128Val	missense	Exon 2 of 3	NP_997329.2	Q3ZCQ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM174B	ENST00000327355.6	TSL:1 MANE Select	c.382A>G	p.Ile128Val	missense	Exon 2 of 3	ENSP00000329040.5	Q3ZCQ3
	FAM174B	ENST00000555064.5	TSL:4	c.-43A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 3	ENSP00000455765.1	G3V5D1
	FAM174B	ENST00000555696.5	TSL:4	c.-43A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 3	ENSP00000456619.1	G3V5D1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000804 AC: 2 AN: 248868 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461476 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727030

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111730

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000434 Hom.: 0

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	Uncertain	0.37
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.010	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.0	L
PhyloP100		7.3
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.20
Sift	Benign	0.14	T
Sift4G	Uncertain	0.030	D
Polyphen		0.99	D
Vest4		0.68
MutPred		0.41		Gain of MoRF binding (P = 0.0992)
MVP		0.030
MPC		1.0
ClinPred		0.61	D
GERP RS		5.4
Varity_R		0.086
gMVP		0.43

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: rs1447683740; hg19: chr15-93173538;