2-241897239-G-T

Variant names:

• chr2-241897239-G-T
• rs757669825
• NM_001382368.1:c.108C>A

Variant summary

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

The NM_001382368.1(FAM240C):​c.108C>A​(p.His36Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,397,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/11 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H36H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: FAM240C NM_001382368.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 0 publications found

Genes affected

FAM240C (HGNC:54200): (family with sequence similarity 240 member C)

LINC01237 (HGNC:49793): (long intergenic non-protein coding RNA 1237)

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=0.09474599).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382368.1. 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
	FAM240C	NM_001382368.1	MANE Select	c.108C>A	p.His36Gln	missense	Exon 2 of 3	NP_001369297.1	A0A1B0GVR7
	FAM240C	NM_001382369.1		c.93C>A	p.His31Gln	missense	Exon 2 of 3	NP_001369298.1	A0A1B0GUP9
	FAM240C	NM_001382370.1		c.93C>A	p.His31Gln	missense	Exon 2 of 3	NP_001369299.1	A0A1B0GUP9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM240C	ENST00000404031.6	TSL:3 MANE Select	c.108C>A	p.His36Gln	missense	Exon 2 of 3	ENSP00000490626.1	A0A1B0GVR7
	FAM240C	ENST00000401641.2	TSL:2	c.93C>A	p.His31Gln	missense	Exon 2 of 3	ENSP00000490196.1	A0A1B0GUP9
	FAM240C	ENST00000452112.5	TSL:5	c.93C>A	p.His31Gln	missense	Exon 2 of 3	ENSP00000490703.2	A0A1B0GUP9

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1397730 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 689356

⚠️ 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: 31592

American (AMR) AF: 0.00 AC: 0 AN: 35676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25156

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078548

Other (OTH) AF: 0.00 AC: 0 AN: 58012

⚠️ 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 Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.093
DANN	Benign	0.93
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0054	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.5
REVEL	Benign	0.0030
GERP RS		-1.6
Mutation Taster		=99/1	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs757669825; hg19: chr2-242839390;