rs766891221

Variant names:

• chr9-35819899-T-A
• rs766891221
• NM_001012446.4:c.844A>T

Your query was ambiguous. Multiple possible variants found:

• chr9-35819899-T-A
• chr9-35819899-T-C
• chr9-35819899-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001012446.4(FAM221B):​c.844A>T​(p.Ile282Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000681 in 146,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000068 (0 hom., cov: 32)
• Consequence: FAM221B NM_001012446.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21907052).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM221B	NM_001012446.4	c.844A>T	p.Ile282Phe	missense_variant	Exon 4 of 7	ENST00000423537.7	NP_001012448.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM221B	ENST00000423537.7	c.844A>T	p.Ile282Phe	missense_variant	Exon 4 of 7	1	NM_001012446.4	ENSP00000415299.2
ENSG00000285645	ENST00000650284.1	n.35A>T		non_coding_transcript_exon_variant	Exon 3 of 10			ENSP00000498023.1

Frequencies

GnomAD3 genomes AF: 0.00000681 AC: 1 AN: 146834 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000154

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000681 AC: 1 AN: 146834 Hom.: 0 Cov.: 32 AF XY: 0.0000139 AC XY: 1 AN XY: 71714

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000154

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.00095	T;.
Eigen	Benign	0.015
Eigen_PC	Benign	0.065
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.064
Sift	Benign	0.15	T;D
Sift4G	Benign	0.38	T;.
Polyphen		0.89	P;.
Vest4		0.48
MutPred		0.36		Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);
MVP		0.16
MPC		0.44
ClinPred		0.69	D
GERP RS		4.2
Varity_R		0.087
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs766891221; hg19: chr9-35819896;