rs243609

Positions:

• chr21-17789372-C-G
• chr21-17789372-C-T
• chr21-17789372-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001100420.2(C21orf91):​c.*4043G>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: 31)
• Consequence: C21orf91 NM_001100420.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.851

Genes affected

C21orf91 (HGNC:16459): (chromosome 21 open reading frame 91) Predicted to be involved in cerebral cortex neuron differentiation and positive regulation of dendritic spine development. [provided by Alliance of Genome Resources, Apr 2022]

C21orf91-OT1 (HGNC:16729): (C21orf91 overlapping transcript 1)

LOC124900465 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C21orf91	NM_001100420.2	c.*4043G>C		3_prime_UTR_variant	5/5	ENST00000284881.9	NP_001093890.1
C21orf91-OT1	NR_038870.1	n.34-2162G>C		intron_variant, non_coding_transcript_variant
LOC124900465	XR_007067823.1	n.1605+32583C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C21orf91	ENST00000284881.9	c.*4043G>C		3_prime_UTR_variant	5/5	2	NM_001100420.2	ENSP00000284881	P4
C21orf91-OT1	ENST00000430401.5	n.34-2162G>C		intron_variant, non_coding_transcript_variant		1
C21orf91-OT1	ENST00000430815.5	n.48-2162G>C		intron_variant, non_coding_transcript_variant		5
C21orf91-OT1	ENST00000439392.1	n.34-2162G>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.15
DANN	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs243609; hg19: chr21-19161689;