22-21644133-C-G

Variant names:

• chr22-21644133-C-G
• rs752791365
• NM_022044.3:c.624C>G

Variant summary

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

The NM_022044.3(SDF2L1):​c.624C>G​(p.Ile208Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SDF2L1 NM_022044.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.03
• Publications: 0 publications found

Genes affected

SDF2L1 (HGNC:10676): (stromal cell derived factor 2 like 1) Enables misfolded protein binding activity. Involved in chaperone cofactor-dependent protein refolding. Located in endoplasmic reticulum. Part of chaperone complex. [provided by Alliance of Genome Resources, Apr 2022]

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=0.2286435).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022044.3. 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
	SDF2L1	NM_022044.3	MANE Select	c.624C>G	p.Ile208Met	missense	Exon 3 of 3	NP_071327.2	Q9HCN8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDF2L1	ENST00000248958.5	TSL:1 MANE Select	c.624C>G	p.Ile208Met	missense	Exon 3 of 3	ENSP00000248958.4	Q9HCN8
	SDF2L1	ENST00000927919.1		c.621C>G	p.Ile207Met	missense	Exon 3 of 3	ENSP00000597978.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461882 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	19
DANN	Benign	0.92
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.030
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.0
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.34
Sift	Benign	0.30	T
Sift4G	Benign	0.26	T
Polyphen		0.24	B
Vest4		0.25
MutPred		0.41		Gain of disorder (P = 0.0209)
MVP		0.82
MPC		1.0
ClinPred		0.60	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.60
Mutation Taster		=71/29	polymorphism

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: rs752791365; hg19: chr22-21998422;