chr4-38905820-C-T

Variant names:

• chr4-38905820-C-T
• rs139789863
• NM_138389.4:c.616C>T

Variant summary

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

The NM_001330764.2(FAM114A1):​c.-6C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000083 (0 hom.)
• Consequence: FAM114A1 NM_001330764.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.56
• Publications: 2 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330764.2. 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.616C>T	p.Arg206Trp	missense	Exon 6 of 15	NP_612398.2	Q8IWE2-1
	FAM114A1	NM_001330764.2		c.-6C>T		5_prime_UTR_premature_start_codon_gain	Exon 5 of 14	NP_001317693.1	Q8IWE2-2
	FAM114A1	NM_001350631.2		c.-6C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 12	NP_001337560.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM114A1	ENST00000358869.5	TSL:1 MANE Select	c.616C>T	p.Arg206Trp	missense	Exon 6 of 15	ENSP00000351740.2	Q8IWE2-1
	FAM114A1	ENST00000515037.5	TSL:2	c.-6C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 13	ENSP00000424115.1	Q8IWE2-2
	FAM114A1	ENST00000903774.1		c.616C>T	p.Arg206Trp	missense	Exon 5 of 15	ENSP00000573833.1

Frequencies

GnomAD3 genomes AF: 0.000322 AC: 49 AN: 152152 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000435

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000163 AC: 41 AN: 251094 AF XY: 0.000125

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000828 AC: 121 AN: 1461770 Hom.: 0 Cov.: 31 AF XY: 0.0000729 AC XY: 53 AN XY: 727200

African (AFR) AF: 0.000329 AC: 11 AN: 33466

American (AMR) AF: 0.000336 AC: 15 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26130

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86250

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000710 AC: 79 AN: 1111980

Other (OTH) AF: 0.0000828 AC: 5 AN: 60384

GnomAD4 genome AF: 0.000322 AC: 49 AN: 152270 Hom.: 0 Cov.: 32 AF XY: 0.000255 AC XY: 19 AN XY: 74460

African (AFR) AF: 0.000433 AC: 18 AN: 41544

American (AMR) AF: 0.000785 AC: 12 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68024

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000218 Hom.: 0

Bravo AF: 0.000317

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000132 AC: 16

EpiCase AF: 0.0000545

EpiControl AF: 0.000237

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	0.15
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.077	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.6
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.32
Sift	Benign	0.037	D
Sift4G	Benign	0.19	T
Polyphen		1.0	D
Vest4		0.71
MVP		0.79
MPC		0.40
ClinPred		0.093	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.050
gMVP		0.67
Mutation Taster		=57/43	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs139789863; hg19: chr4-38907441;