19-35225196-C-A

Variant names:

• chr19-35225196-C-A
• rs1298961456
• NM_152481.2:c.739G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152481.2(FAM187B):​c.739G>T​(p.Ala247Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000074 in 1,350,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. A247T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: FAM187B NM_152481.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.543
• Publications: 0 publications found

Genes affected

FAM187B (HGNC:26366): (family with sequence similarity 187 member B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29183298).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152481.2. 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
	FAM187B	NM_152481.2	MANE Select	c.739G>T	p.Ala247Ser	missense	Exon 2 of 2	NP_689694.1	Q17R55

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM187B	ENST00000324675.4	TSL:1 MANE Select	c.739G>T	p.Ala247Ser	missense	Exon 2 of 2	ENSP00000323355.3	Q17R55

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.40e-7 AC: 1 AN: 1350530 Hom.: 0 Cov.: 31 AF XY: 0.00000152 AC XY: 1 AN XY: 659266

African (AFR) AF: 0.00 AC: 0 AN: 30684

American (AMR) AF: 0.00 AC: 0 AN: 27608

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20118

East Asian (EAS) AF: 0.00 AC: 0 AN: 37764

South Asian (SAS) AF: 0.00 AC: 0 AN: 69394

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5240

European-Non Finnish (NFE) AF: 9.46e-7 AC: 1 AN: 1056674

Other (OTH) AF: 0.00 AC: 0 AN: 55732

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0061	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.54
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.13
Sift	Benign	0.058	T
Sift4G	Uncertain	0.044	D
Polyphen		0.85	P
Vest4		0.11
MutPred		0.74		Gain of relative solvent accessibility (P = 0.0023)
MVP		0.34
MPC		0.80
ClinPred		0.53	D
GERP RS		1.8
Varity_R		0.072
gMVP		0.53
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: rs1298961456; hg19: chr19-35716099;