chr9-112063019-C-T

Variant names:

• chr9-112063019-C-T
• rs80215167
• NM_022486.5:c.1768G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_022486.5(SUSD1):​c.1768G>A​(p.Glu590Lys) 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 1,612,074 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0032 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0055 (28 hom.)
• Consequence: SUSD1 NM_022486.5 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.92
• Publications: 11 publications found

Genes affected

SUSD1 (HGNC:25413): (sushi domain containing 1) Predicted to enable calcium ion binding activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0107268095).
• BP6: Variant 9-112063019-C-T is Benign according to our data. Variant chr9-112063019-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 770751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022486.5. 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
	SUSD1	NM_022486.5	MANE Select	c.1768G>A	p.Glu590Lys	missense	Exon 13 of 17	NP_071931.2
	SUSD1	NM_001282640.2		c.1768G>A	p.Glu590Lys	missense	Exon 13 of 18	NP_001269569.1	Q6UWL2-2
	SUSD1	NM_001282643.2		c.1768G>A	p.Glu590Lys	missense	Exon 13 of 16	NP_001269572.1	F8WAQ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUSD1	ENST00000374270.8	TSL:1 MANE Select	c.1768G>A	p.Glu590Lys	missense	Exon 13 of 17	ENSP00000363388.4	Q6UWL2-1
	SUSD1	ENST00000374264.6	TSL:1	c.1768G>A	p.Glu590Lys	missense	Exon 13 of 18	ENSP00000363382.2	Q6UWL2-2
	SUSD1	ENST00000861057.1		c.1765G>A	p.Glu589Lys	missense	Exon 13 of 17	ENSP00000531116.1

Frequencies

GnomAD3 genomes AF: 0.00322 AC: 490 AN: 152128 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000893

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00539

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00581

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00348 AC: 873 AN: 250892 AF XY: 0.00365

Gnomad AFR exome AF: 0.000862

Gnomad AMR exome AF: 0.00200

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000417

Gnomad NFE exome AF: 0.00540

Gnomad OTH exome AF: 0.00344

GnomAD4 exome AF: 0.00553 AC: 8071 AN: 1459828 Hom.: 28 Cov.: 28 AF XY: 0.00549 AC XY: 3989 AN XY: 726372

African (AFR) AF: 0.00108 AC: 36 AN: 33432

American (AMR) AF: 0.00186 AC: 83 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00507 AC: 437 AN: 86194

European-Finnish (FIN) AF: 0.000656 AC: 35 AN: 53350

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5764

European-Non Finnish (NFE) AF: 0.00647 AC: 7186 AN: 1110286

Other (OTH) AF: 0.00462 AC: 279 AN: 60338

GnomAD4 genome AF: 0.00322 AC: 490 AN: 152246 Hom.: 3 Cov.: 32 AF XY: 0.00278 AC XY: 207 AN XY: 74446

African (AFR) AF: 0.000891 AC: 37 AN: 41538

American (AMR) AF: 0.00170 AC: 26 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00581 AC: 28 AN: 4818

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00579 AC: 394 AN: 68010

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00498 Hom.: 10

Bravo AF: 0.00305

TwinsUK AF: 0.00728 AC: 27

ALSPAC AF: 0.00778 AC: 30

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00605 AC: 52

ExAC AF: 0.00348 AC: 423

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.00616

EpiControl AF: 0.00552

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.9
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.21
Sift	Benign	0.11	T
Sift4G	Benign	0.19	T
Polyphen		0.99	D
Vest4		0.54
MVP		0.21
MPC		0.72
ClinPred		0.019	T
GERP RS		4.2
Varity_R		0.16
gMVP		0.48
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs80215167; hg19: chr9-114825299;