chr2-24190604-C-A

Variant names:

• chr2-24190604-C-A
• rs146891535
• NM_001040710.3:c.594C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001040710.3(FAM228A):​c.594C>A​(p.His198Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000604 in 1,588,498 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000063 (1 hom.)
• Consequence: FAM228A NM_001040710.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.473
• Publications: 1 publications found

Genes affected

FAM228A (HGNC:34418): (family with sequence similarity 228 member A)

ENSG00000276087 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08441481).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040710.3. 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
	FAM228A	NM_001040710.3	MANE Select	c.594C>A	p.His198Gln	missense	Exon 6 of 6	NP_001035800.1	Q86W67

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM228A	ENST00000295150.8	TSL:1 MANE Select	c.594C>A	p.His198Gln	missense	Exon 6 of 6	ENSP00000295150.3	Q86W67
	FAM228A	ENST00000965618.1		c.525C>A	p.His175Gln	missense	Exon 5 of 5	ENSP00000635677.1
	FAM228A	ENST00000432434.2	TSL:5	c.660+51C>A		intron	N/A	ENSP00000412833.2	H7C3M9

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152102 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000665 AC: 15 AN: 225534 AF XY: 0.0000574

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000135

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000572

Gnomad OTH exome AF: 0.000185

GnomAD4 exome AF: 0.0000634 AC: 91 AN: 1436396 Hom.: 1 Cov.: 32 AF XY: 0.0000659 AC XY: 47 AN XY: 713036

African (AFR) AF: 0.00 AC: 0 AN: 32128

American (AMR) AF: 0.000202 AC: 8 AN: 39670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24560

East Asian (EAS) AF: 0.00 AC: 0 AN: 39490

South Asian (SAS) AF: 0.000195 AC: 16 AN: 82022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52710

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5202

European-Non Finnish (NFE) AF: 0.0000590 AC: 65 AN: 1101434

Other (OTH) AF: 0.0000338 AC: 2 AN: 59180

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152102 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74278

African (AFR) AF: 0.00 AC: 0 AN: 41428

American (AMR) AF: 0.000262 AC: 4 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000189 Hom.: 0

Bravo AF: 0.000117

ExAC AF: 0.0000579 AC: 7

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	0.11
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.080
DANN	Benign	0.49
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.47
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.32	N
REVEL	Benign	0.15
Sift	Benign	0.051	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.92	P
Vest4		0.12
MutPred		0.13		Gain of relative solvent accessibility (P = 0.1066)
MVP		0.048
MPC		0.057
ClinPred		0.42	T
GERP RS		-4.3
Varity_R		0.034
gMVP		0.011
Mutation Taster		=99/1	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: rs146891535; hg19: chr2-24413473;