21-17789198-A-C

Variant names:

• chr21-17789198-A-C
• rs243607
• NM_001100420.2:c.*4217T>G

Variant summary

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

The NM_001100420.2(C21orf91):​c.*4217T>G variant causes a 3 prime UTR change. 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: 30)
• Consequence: C21orf91 NM_001100420.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.71
• Publications: 10 publications found

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)

ENSG00000244676 (HGNC:):

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=-0.71).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100420.2. 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
	C21orf91	NM_001100420.2	MANE Select	c.*4217T>G		3_prime_UTR	Exon 5 of 5	NP_001093890.1
	C21orf91	NM_017447.4		c.*4217T>G		3_prime_UTR	Exon 5 of 5	NP_059143.3
	C21orf91	NM_001100421.2		c.*4382T>G		3_prime_UTR	Exon 4 of 4	NP_001093891.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C21orf91	ENST00000284881.9	TSL:2 MANE Select	c.*4217T>G		3_prime_UTR	Exon 5 of 5	ENSP00000284881.4
	C21orf91-OT1	ENST00000430401.5	TSL:1	n.34-1988T>G		intron	N/A
	C21orf91-OT1	ENST00000439392.1	TSL:1	n.34-1988T>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 22078

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	16
DANN	Benign	0.86
PhyloP100		3.7

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: rs243607; hg19: chr21-19161515;