9-35819374-C-G

Variant names:

• chr9-35819374-C-G
• NM_001012446.4:c.874G>C
• FAM221B p.Val292Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001012446.4(FAM221B):​c.874G>C​(p.Val292Leu) variant causes a missense 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. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM221B NM_001012446.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190
• Publications: 0 publications found

Genes affected

FAM221B (HGNC:30762): (family with sequence similarity 221 member B)

ENSG00000285645 (HGNC:):

TMEM8B (HGNC:21427): (transmembrane protein 8B) Involved in cell-matrix adhesion. Located in cell surface and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08035755).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012446.4. 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
	FAM221B	NM_001012446.4	MANE Select	c.874G>C	p.Val292Leu	missense	Exon 5 of 7	NP_001012448.2	A6H8Z2-1
	FAM221B	NR_052026.2		n.1335G>C		non_coding_transcript_exon	Exon 6 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM221B	ENST00000423537.7	TSL:1 MANE Select	c.874G>C	p.Val292Leu	missense	Exon 5 of 7	ENSP00000415299.2	A6H8Z2-1
	FAM221B	ENST00000377984.2	TSL:1	c.874G>C	p.Val292Leu	missense	Exon 6 of 6	ENSP00000367222.2	F8W8N9
	FAM221B	ENST00000388950.8	TSL:1	n.*42G>C		non_coding_transcript_exon	Exon 6 of 8	ENSP00000373602.4	A6H8Z2-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.019
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.053
Sift	Benign	0.045	D
Sift4G	Benign	0.43	T
Varity_R		0.053
gMVP		0.34
Mutation Taster		=98/2	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr9-35819371;