4-38891777-C-G

Variant names:

• chr4-38891777-C-G
• rs1579319630
• NM_138389.4:c.383C>G

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.383C>G​(p.Ala128Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,459,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A128V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: FAM114A1 NM_138389.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15
• 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=0.09502256).

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.383C>G	p.Ala128Gly	missense	Exon 4 of 15	NP_612398.2	Q8IWE2-1
	FAM114A1	NM_001375792.1		c.383C>G	p.Ala128Gly	missense	Exon 3 of 14	NP_001362721.1	Q8IWE2-1
	FAM114A1	NM_001350632.2		c.383C>G	p.Ala128Gly	missense	Exon 3 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.383C>G	p.Ala128Gly	missense	Exon 4 of 15	ENSP00000351740.2	Q8IWE2-1
	FAM114A1	ENST00000903774.1		c.383C>G	p.Ala128Gly	missense	Exon 3 of 15	ENSP00000573833.1
	FAM114A1	ENST00000967134.1		c.383C>G	p.Ala128Gly	missense	Exon 4 of 16	ENSP00000637193.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1459986 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726280

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44318

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39578

South Asian (SAS) AF: 0.00 AC: 0 AN: 85936

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111200

Other (OTH) AF: 0.00 AC: 0 AN: 60294

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	19
DANN	Benign	0.90
DEOGEN2	Benign	0.00069	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.63	N
PhyloP100		2.1
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.33	N
REVEL	Benign	0.11
Sift	Benign	0.74	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.012	B
Vest4		0.21
MutPred		0.52		Gain of glycosylation at S132 (P = 0.0219)
MVP		0.39
MPC		0.070
ClinPred		0.28	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.048
gMVP		0.17
Mutation Taster		=66/34	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1579319630; hg19: chr4-38893398;