chr1-16059892-A-G

Variant names:

• chr1-16059892-A-G
• rs755874200
• NM_182623.3:c.428T>C

Variant summary

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

The NM_182623.3(FAM131C):​c.428T>C​(p.Leu143Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000025 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM131C NM_182623.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.43
• 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.

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.428T>C	p.Leu143Pro	missense	Exon 5 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.428T>C	p.Leu143Pro	missense	Exon 5 of 7	ENSP00000364814.4	Q96AQ9
	FAM131C	ENST00000943020.1		c.392T>C	p.Leu131Pro	missense	Exon 4 of 6	ENSP00000613079.1
	FAM131C	ENST00000904375.1		c.269-288T>C		intron	N/A	ENSP00000574434.1

Frequencies

GnomAD3 genomes AF: 0.000277 AC: 12 AN: 43248 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00403

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000795

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 247916 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000332

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000250 AC: 31 AN: 1240268 Hom.: 0 Cov.: 49 AF XY: 0.0000212 AC XY: 13 AN XY: 612412

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30886

American (AMR) AF: 0.0000866 AC: 3 AN: 34642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19672

East Asian (EAS) AF: 0.00 AC: 0 AN: 15290

South Asian (SAS) AF: 0.00 AC: 0 AN: 66386

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39804

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3512

European-Non Finnish (NFE) AF: 0.0000244 AC: 24 AN: 982420

Other (OTH) AF: 0.0000839 AC: 4 AN: 47656

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000277 AC: 12 AN: 43354 Hom.: 0 Cov.: 0 AF XY: 0.000285 AC XY: 6 AN XY: 21024

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 23584

American (AMR) AF: 0.00403 AC: 11 AN: 2732

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 662

East Asian (EAS) AF: 0.00 AC: 0 AN: 302

South Asian (SAS) AF: 0.00 AC: 0 AN: 610

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 66

European-Non Finnish (NFE) AF: 0.0000795 AC: 1 AN: 12586

Other (OTH) AF: 0.00 AC: 0 AN: 538

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000826 AC: 1

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	Pathogenic	0.84
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.054	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.061	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.4
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.26
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.031	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.48		Gain of disorder (P = 0.0166)
MVP		0.51
MPC		1.6
ClinPred		0.89	D
GERP RS		4.7
Varity_R		0.68
gMVP		0.64
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs755874200; hg19: chr1-16386387;