4-38922860-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138389.4(FAM114A1):c.1036G>A(p.Glu346Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM114A1 NM_138389.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.52

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22119075).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM114A1	NM_138389.4	c.1036G>A	p.Glu346Lys	missense_variant	9/15	ENST00000358869.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM114A1	ENST00000358869.5	c.1036G>A	p.Glu346Lys	missense_variant	9/15	1	NM_138389.4	P1
FAM114A1	ENST00000515037.5	c.415G>A	p.Glu139Lys	missense_variant	7/13	2
FAM114A1	ENST00000512889.1	n.546G>A		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2021

The c.1036G>A (p.E346K) alteration is located in exon 9 (coding exon 7) of the FAM114A1 gene. This alteration results from a G to A substitution at nucleotide position 1036, causing the glutamic acid (E) at amino acid position 346 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
Cadd	Pathogenic	29
Dann	Pathogenic	1.0
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.76	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Benign	0.18
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.013	D;D
Polyphen		0.98	.;D
Vest4		0.31
MutPred		0.38		.;Gain of ubiquitination at E346 (P = 0.0022);
MVP		0.57
MPC		0.25
ClinPred		0.95	D
GERP RS		5.8
Varity_R		0.32
gMVP		0.43

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-38924481;