15-92630345-C-T

Variant names:

• chr15-92630345-C-T
• rs1567044423
• NM_207446.3:c.345G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_207446.3(FAM174B):​c.345G>A​(p.Arg115Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: FAM174B NM_207446.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.005601
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.42
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 15-92630345-C-T is Benign according to our data. Variant chr15-92630345-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3847455.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=3.42 with no splicing effect.

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.345G>A	p.Arg115Arg	splice_region synonymous	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.345G>A	p.Arg115Arg	splice_region synonymous	Exon 2 of 3	ENSP00000329040.5	Q3ZCQ3
	FAM174B	ENST00000555064.5	TSL:4	c.-80G>A		splice_region	Exon 2 of 3	ENSP00000455765.1	G3V5D1
	FAM174B	ENST00000555696.5	TSL:4	c.-80G>A		splice_region	Exon 2 of 3	ENSP00000456619.1	G3V5D1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.7
DANN	Benign	0.64
PhyloP100		3.4

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0056
dbscSNV1_RF	Benign	0.29
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: rs1567044423; hg19: chr15-93173575;