NM_138389.4:c.230C>T

Variant names:

• chr4-38878308-C-T
• rs1015231539
• NM_138389.4:c.230C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138389.4(FAM114A1):​c.230C>T​(p.Ala77Val) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A77T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM114A1 NM_138389.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.20
• Publications: 0 publications found

Genes affected

FAM114A1 (HGNC:25087): (family with sequence similarity 114 member A1) The protein encoded by this gene belongs to the FAM114 family and may play a role in neuronal cell development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08202657).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138389.4. 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
	FAM114A1	NM_138389.4	MANE Select	c.230C>T	p.Ala77Val	missense	Exon 3 of 15	NP_612398.2	Q8IWE2-1
	FAM114A1	NM_001375792.1		c.230C>T	p.Ala77Val	missense	Exon 2 of 14	NP_001362721.1	Q8IWE2-1
	FAM114A1	NM_001350632.2		c.230C>T	p.Ala77Val	missense	Exon 2 of 14	NP_001337561.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM114A1	ENST00000358869.5	TSL:1 MANE Select	c.230C>T	p.Ala77Val	missense	Exon 3 of 15	ENSP00000351740.2	Q8IWE2-1
	FAM114A1	ENST00000903774.1		c.230C>T	p.Ala77Val	missense	Exon 2 of 15	ENSP00000573833.1
	FAM114A1	ENST00000967134.1		c.230C>T	p.Ala77Val	missense	Exon 3 of 16	ENSP00000637193.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	0.069
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	10
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PhyloP100		1.2
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.046
Sift	Benign	0.29	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.076
MutPred		0.12		Loss of glycosylation at P80 (P = 0.1262)
MVP		0.46
MPC		0.065
ClinPred		0.081	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.026
gMVP		0.094
Mutation Taster		=91/9	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: rs1015231539; hg19: chr4-38879929;