rs141756767

Variant names:

• chr10-122850432-G-C
• rs141756767
• NM_152644.3:c.84C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-122850432-G-C
• chr10-122850432-G-A

Variant summary

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

The NM_152644.3(FAM24B):​c.84C>G​(p.Asn28Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: FAM24B NM_152644.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.81
• Publications: 1 publications found

Genes affected

FAM24B (HGNC:23475): (family with sequence similarity 24 member B) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286088 (HGNC:):

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=0.024696052).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152644.3. 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
	FAM24B	NM_152644.3	MANE Select	c.84C>G	p.Asn28Lys	missense	Exon 3 of 4	NP_689857.2	Q8N5W8
	FAM24B	NM_001204364.1		c.84C>G	p.Asn28Lys	missense	Exon 3 of 4	NP_001191293.1	Q8N5W8
	FAM24B	NR_037911.1		n.300-993C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM24B	ENST00000368898.8	TSL:1 MANE Select	c.84C>G	p.Asn28Lys	missense	Exon 3 of 4	ENSP00000357894.3	Q8N5W8
	ENSG00000286088	ENST00000368904.6	TSL:1	n.-377-4212C>G		intron	N/A	ENSP00000357900.2	A0A499FIG0
	FAM24B	ENST00000368896.1	TSL:2	c.84C>G	p.Asn28Lys	missense	Exon 3 of 4	ENSP00000357892.1	Q8N5W8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251398 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

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 AF: 0.00000684 AC: 10 AN: 1461296 Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7 AN XY: 726998

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111472

Other (OTH) AF: 0.0000166 AC: 1 AN: 60382

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.14
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.0020
DANN	Benign	0.54
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.8
PrimateAI	Benign	0.28	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.020
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.017	B
Vest4		0.077
MutPred		0.27		Gain of methylation at N28 (P = 0.012)
MVP		0.10
MPC		0.29
ClinPred		0.063	T
GERP RS		-5.9
Varity_R		0.031
gMVP		0.032
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs141756767; hg19: chr10-124609948;