rs1048455

Variant names:

• chr5-141641157-T-G
• rs1048455
• NM_033449.3:c.*341A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033449.3(FCHSD1):​c.*341A>C variant causes a 3 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FCHSD1 NM_033449.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.979
• Publications: 0 publications found

Genes affected

FCHSD1 (HGNC:25463): (FCH and double SH3 domains 1) Predicted to enable lipid binding activity. Predicted to be involved in neuromuscular synaptic transmission and positive regulation of actin filament polymerization. Predicted to be located in cell projection and perikaryon. Predicted to be active in neuromuscular junction and recycling endosome. Predicted to colocalize with cuticular plate. [provided by Alliance of Genome Resources, Apr 2022]

RELL2 (HGNC:26902): (RELT like 2) Predicted to enable collagen binding activity. Involved in positive regulation of p38MAPK cascade. Predicted to be located in extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033449.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCHSD1	NM_033449.3	MANE Select	c.*341A>C		3_prime_UTR	Exon 20 of 20	NP_258260.1
	RELL2	NM_173828.5	MANE Select	c.*488T>G		downstream_gene	N/A	NP_776189.3
	RELL2	NM_001130029.2		c.*488T>G		downstream_gene	N/A	NP_001123501.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCHSD1	ENST00000435817.7	TSL:1 MANE Select	c.*341A>C		3_prime_UTR	Exon 20 of 20	ENSP00000399259.2
	FCHSD1	ENST00000896539.1		c.*341A>C		3_prime_UTR	Exon 20 of 20	ENSP00000566598.1
	FCHSD1	ENST00000896537.1		c.*341A>C		3_prime_UTR	Exon 20 of 20	ENSP00000566596.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 178288 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 90046

African (AFR) AF: 0.00 AC: 0 AN: 5858

American (AMR) AF: 0.00 AC: 0 AN: 7360

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6674

East Asian (EAS) AF: 0.00 AC: 0 AN: 15346

South Asian (SAS) AF: 0.00 AC: 0 AN: 4144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 930

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 113688

Other (OTH) AF: 0.00 AC: 0 AN: 11926

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.88
PhyloP100		0.98

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: rs1048455; hg19: chr5-141020724;