1-16058579-G-T

Variant names:

• chr1-16058579-G-T
• rs752539505
• NM_182623.3:c.701C>A

Variant summary

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

The NM_182623.3(FAM131C):​c.701C>A​(p.Pro234Gln) 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. 14/22 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. P234L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 44)
• Consequence: FAM131C NM_182623.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176
• Publications: 0 publications found

Genes affected

FAM131C (HGNC:26717): (family with sequence similarity 131 member C)

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=0.14434505).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182623.3. 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
	FAM131C	NM_182623.3	MANE Select	c.701C>A	p.Pro234Gln	missense	Exon 7 of 7	NP_872429.2	Q96AQ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM131C	ENST00000375662.5	TSL:1 MANE Select	c.701C>A	p.Pro234Gln	missense	Exon 7 of 7	ENSP00000364814.4	Q96AQ9
	FAM131C	ENST00000943020.1		c.665C>A	p.Pro222Gln	missense	Exon 6 of 6	ENSP00000613079.1
	FAM131C	ENST00000904375.1		c.518C>A	p.Pro173Gln	missense	Exon 6 of 6	ENSP00000574434.1

Frequencies

GnomAD3 genomes Cov.: 44

GnomAD4 exome Cov.: 88

GnomAD4 genome Cov.: 44

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	9.1
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0069	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	M
PhyloP100		-0.18
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.075
Sift	Benign	0.046	D
Sift4G	Benign	0.19	T
Polyphen		0.94	P
Vest4		0.070
MutPred		0.15		Loss of glycosylation at S238 (P = 0.1085)
MVP		0.22
MPC		1.0
ClinPred		0.46	T
GERP RS		2.8
Varity_R		0.029
gMVP		0.21
Mutation Taster		=98/2	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: rs752539505; hg19: chr1-16385074;