NM_152481.2:c.727G>A

Variant names:

• chr19-35225208-C-T
• rs774839114
• NM_152481.2:c.727G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_152481.2(FAM187B):​c.727G>A​(p.Val243Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000448 in 1,340,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V243L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000045 (0 hom.)
• Consequence: FAM187B NM_152481.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.959
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10310584).
• BP6: Variant 19-35225208-C-T is Benign according to our data. Variant chr19-35225208-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3512020.Status of the report is criteria_provided_single_submitter, 1 stars.

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.727G>A	p.Val243Ile	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.727G>A	p.Val243Ile	missense	Exon 2 of 2	ENSP00000323355.3	Q17R55

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000336 AC: 4 AN: 118878 AF XY: 0.0000164

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: 0.0000828

Gnomad NFE exome AF: 0.0000579

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000448 AC: 6 AN: 1340202 Hom.: 0 Cov.: 31 AF XY: 0.00000459 AC XY: 3 AN XY: 653702

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30376

American (AMR) AF: 0.00 AC: 0 AN: 25916

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19804

East Asian (EAS) AF: 0.00 AC: 0 AN: 37354

South Asian (SAS) AF: 0.00 AC: 0 AN: 68168

European-Finnish (FIN) AF: 0.0000431 AC: 2 AN: 46360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5052

European-Non Finnish (NFE) AF: 0.00000380 AC: 4 AN: 1051888

Other (OTH) AF: 0.00 AC: 0 AN: 55284

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0241431), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.076
DANN	Benign	0.92
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.29	N
PhyloP100		-0.96
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.078
Sift	Benign	0.25	T
Sift4G	Benign	0.55	T
Polyphen		0.74	P
Vest4		0.14
MutPred		0.57		Loss of sheet (P = 0.0817)
MVP		0.099
MPC		0.22
ClinPred		0.051	T
GERP RS		-5.0
Varity_R		0.029
gMVP		0.33
Mutation Taster		=100/0	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: rs774839114; hg19: chr19-35716111;