rs1180787235

Variant names:

• chr5-153997846-G-A
• rs1180787235
• NM_018691.4:c.1286C>T

Variant summary

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

The NM_018691.4(FAM114A2):​c.1286C>T​(p.Ser429Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,453,114 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FAM114A2 NM_018691.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.24
• Publications: 0 publications found

Genes affected

FAM114A2 (HGNC:1333): (family with sequence similarity 114 member A2)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018691.4. 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
	FAM114A2	NM_018691.4	MANE Select	c.1286C>T	p.Ser429Phe	missense	Exon 12 of 14	NP_061161.2	A0A140VKG4
	FAM114A2	NM_001317993.2		c.1286C>T	p.Ser429Phe	missense	Exon 13 of 15	NP_001304922.1	Q9NRY5
	FAM114A2	NM_001317994.2		c.1286C>T	p.Ser429Phe	missense	Exon 12 of 14	NP_001304923.1	A0A140VKG4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM114A2	ENST00000351797.9	TSL:1 MANE Select	c.1286C>T	p.Ser429Phe	missense	Exon 12 of 14	ENSP00000341597.4	Q9NRY5
	FAM114A2	ENST00000520667.5	TSL:1	c.1286C>T	p.Ser429Phe	missense	Exon 13 of 15	ENSP00000430384.1	Q9NRY5
	FAM114A2	ENST00000522858.5	TSL:1	c.1286C>T	p.Ser429Phe	missense	Exon 12 of 14	ENSP00000430489.1	Q9NRY5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1453114 Hom.: 0 Cov.: 26 AF XY: 0.00000138 AC XY: 1 AN XY: 723520

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33286

American (AMR) AF: 0.00 AC: 0 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.00 AC: 0 AN: 85882

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1104414

Other (OTH) AF: 0.00 AC: 0 AN: 60060

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.22
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		4.2
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.20
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.99	D
Vest4		0.66
MutPred		0.33		Loss of disorder (P = 0.0168)
MVP		0.41
MPC		0.16
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.50
gMVP		0.67
Mutation Taster		=74/26	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: rs1180787235; hg19: chr5-153377406;