rs1047978

chr21-17796838-G-Tchr21-17796838-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001100420.2(C21orf91):c.408C>A(p.Asp136Glu) variant causes a missense 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency: Genomes: not found (cov: 33)
• Consequence: C21orf91 NM_001100420.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.915

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38547498).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C21orf91	NM_001100420.2	c.408C>A	p.Asp136Glu	missense_variant	3/5	ENST00000284881.9
LOC124900465	XR_007067823.1	n.1605+40049G>T		intron_variant, non_coding_transcript_variant
C21orf91	NM_017447.4	c.408C>A	p.Asp136Glu	missense_variant	3/5
C21orf91	NM_001100421.2	c.408C>A	p.Asp136Glu	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C21orf91	ENST00000284881.9	c.408C>A	p.Asp136Glu	missense_variant	3/5	2	NM_001100420.2	P4
	ENST00000428689.5	n.71+3280G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
Cadd	Benign	20
Dann	Uncertain	1.0
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.81	T;T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.39	T;T;T;T
MetaSVM	Benign	-0.87	T
MutationTaster	Benign	0.0092	P;P
PROVEAN	Uncertain	-3.1	D;D;N;N
REVEL	Benign	0.14
Sift	Benign	0.053	T;D;D;D
Sift4G	Uncertain	0.020	D;D;D;.
Vest4		0.25
MutPred		0.34		Gain of disorder (P = 0.1272);Gain of disorder (P = 0.1272);Gain of disorder (P = 0.1272);Gain of disorder (P = 0.1272);
MVP		0.25
MPC		0.55
ClinPred		0.95	D
GERP RS		3.4
gMVP		0.35

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: rs1047978; hg19: chr21-19169155;