rs199971746

Variant names:

• chr15-49371309-G-A
• rs199971746
• NM_152647.3:c.1103C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-49371309-G-A
• chr15-49371309-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152647.3(FAM227B):​c.1103C>T​(p.Ala368Val) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A368E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM227B NM_152647.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 0 publications found

Genes affected

FAM227B (HGNC:26543): (family with sequence similarity 227 member B)

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=0.056440204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM227B	NM_152647.3	c.1103C>T	p.Ala368Val	missense_variant	Exon 12 of 16	ENST00000299338.11	NP_689860.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM227B	ENST00000299338.11	c.1103C>T	p.Ala368Val	missense_variant	Exon 12 of 16	2	NM_152647.3	ENSP00000299338.6
FAM227B	ENST00000559573.3	n.413C>T		non_coding_transcript_exon_variant	Exon 3 of 5	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 243678 AF XY: 0.00

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: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1422678 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 709652

African (AFR) AF: 0.00 AC: 0 AN: 32232

American (AMR) AF: 0.00 AC: 0 AN: 43302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25774

East Asian (EAS) AF: 0.00 AC: 0 AN: 38926

South Asian (SAS) AF: 0.00 AC: 0 AN: 83698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5494

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1081176

Other (OTH) AF: 0.00 AC: 0 AN: 58986

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.78
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.1
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.014
Sift	Benign	0.20	T
Sift4G	Benign	0.17	T
Polyphen		0.0040	B
Vest4		0.033
MutPred		0.24		Gain of loop (P = 0.0097);
MVP		0.014
MPC		0.045
ClinPred		0.043	T
GERP RS		2.1
Varity_R		0.033
gMVP		0.14
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs199971746; hg19: chr15-49663506; COSMIC: COSV100175476; COSMIC: COSV100175476;