rs867967855

Variant names:

• chr7-3301644-C-G
• rs867967855
• NM_152744.4:c.58C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-3301644-C-G
• chr7-3301644-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_152744.4(SDK1):​c.58C>G​(p.Pro20Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00531 in 977,122 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P20S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.016 (53 hom., cov: 29)
  • Exomes 𝑓: 0.0035 (24 hom.)
• Consequence: SDK1 NM_152744.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.319
• Publications: 1 publications found

Genes affected

SDK1 (HGNC:19307): (sidekick cell adhesion molecule 1) The protein encoded by this gene is a member of the immunoglobulin superfamily. The protein contains six immunoglobulin-like domains and thirteen fibronectin type III domains. Fibronectin type III domains are present in both extracellular and intracellular proteins and tandem repeats are known to contain binding sites for DNA, heparin and the cell surface. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

SDK1-AS1 (HGNC:40883): (SDK1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005708307).
• BP6: Variant 7-3301644-C-G is Benign according to our data. Variant chr7-3301644-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2342528.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.016 (2315/144500) while in subpopulation AFR AF = 0.0464 (1874/40384). AF 95% confidence interval is 0.0447. There are 53 homozygotes in GnomAd4. There are 1126 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 53 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152744.4. 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
	SDK1	NM_152744.4	MANE Select	c.58C>G	p.Pro20Ala	missense	Exon 1 of 45	NP_689957.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDK1	ENST00000404826.7	TSL:1 MANE Select	c.58C>G	p.Pro20Ala	missense	Exon 1 of 45	ENSP00000385899.2	Q7Z5N4-1
	SDK1	ENST00000389531.7	TSL:5	c.58C>G	p.Pro20Ala	missense	Exon 1 of 44	ENSP00000374182.3	F8W6X9
	SDK1-AS1	ENST00000437354.2	TSL:3	n.224+585G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0160 AC: 2319 AN: 144510 Hom.: 53 Cov.: 29

Gnomad AFR AF: 0.0465

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00867

Gnomad ASJ AF: 0.0113

Gnomad EAS AF: 0.000205

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.000246

Gnomad MID AF: 0.00333

Gnomad NFE AF: 0.00275

Gnomad OTH AF: 0.0111

GnomAD4 exome AF: 0.00345 AC: 2875 AN: 832622 Hom.: 24 Cov.: 28 AF XY: 0.00337 AC XY: 1295 AN XY: 384558

African (AFR) AF: 0.0461 AC: 727 AN: 15760

American (AMR) AF: 0.00305 AC: 3 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.0122 AC: 63 AN: 5148

East Asian (EAS) AF: 0.00 AC: 0 AN: 3628

South Asian (SAS) AF: 0.0175 AC: 291 AN: 16644

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 276

Middle Eastern (MID) AF: 0.00681 AC: 11 AN: 1616

European-Non Finnish (NFE) AF: 0.00210 AC: 1601 AN: 761282

Other (OTH) AF: 0.00656 AC: 179 AN: 27284

GnomAD4 genome AF: 0.0160 AC: 2315 AN: 144500 Hom.: 53 Cov.: 29 AF XY: 0.0160 AC XY: 1126 AN XY: 70218

African (AFR) AF: 0.0464 AC: 1874 AN: 40384

American (AMR) AF: 0.00860 AC: 126 AN: 14658

Ashkenazi Jewish (ASJ) AF: 0.0113 AC: 38 AN: 3368

East Asian (EAS) AF: 0.000205 AC: 1 AN: 4870

South Asian (SAS) AF: 0.0152 AC: 72 AN: 4732

European-Finnish (FIN) AF: 0.000246 AC: 2 AN: 8126

Middle Eastern (MID) AF: 0.00362 AC: 1 AN: 276

European-Non Finnish (NFE) AF: 0.00275 AC: 179 AN: 65182

Other (OTH) AF: 0.0110 AC: 22 AN: 2002

Alfa AF: 0.0103 Hom.: 8

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.060
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	3.6
DANN	Benign	0.83
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.44	T
M_CAP	Pathogenic	0.33	D
MetaRNN	Benign	0.0057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.32
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.055
Sift	Pathogenic	0.0	D
Polyphen		0.56	P
Vest4		0.12
MVP		0.60
MPC		0.067
ClinPred		0.098	T
GERP RS		1.5
PromoterAI		0.039	Neutral
Varity_R		0.064
gMVP		0.062
Mutation Taster		=100/0	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: rs867967855; hg19: chr7-3341276;