4-38878085-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.7G>A(p.Asp3Asn) 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: 33)
• Consequence: FAM114A1 NM_138389.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.68

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=0.21547869).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM114A1	NM_138389.4	c.7G>A	p.Asp3Asn	missense_variant	3/15	ENST00000358869.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM114A1	ENST00000358869.5	c.7G>A	p.Asp3Asn	missense_variant	3/15	1	NM_138389.4	P1
FAM114A1	ENST00000510213.5	c.7G>A	p.Asp3Asn	missense_variant	2/3	2
FAM114A1	ENST00000515037.5	c.-274+10251G>A		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Aug 28, 2023

The c.7G>A (p.D3N) alteration is located in exon 3 (coding exon 1) of the FAM114A1 gene. This alteration results from a G to A substitution at nucleotide position 7, causing the aspartic acid (D) at amino acid position 3 to be replaced by an asparagine (N). 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	0.083
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
Cadd	Uncertain	25
Dann	Uncertain	1.0
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.61	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	0.93	D;D
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.6	D;N
REVEL	Benign	0.078
Sift	Uncertain	0.0070	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.73	.;P
Vest4		0.21
MutPred		0.11		Gain of glycosylation at S2 (P = 0.0178);Gain of glycosylation at S2 (P = 0.0178);
MVP		0.57
MPC		0.28
ClinPred		0.90	D
GERP RS		4.7
Varity_R		0.11
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: chr4-38879706;