6-166324574-C-G

Variant names:

• chr6-166324574-C-G
• rs201368298
• NM_145169.3:c.373G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_145169.3(SFT2D1):​c.373G>C​(p.Val125Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000211 in 1,613,020 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00021 (3 hom.)
• Consequence: SFT2D1 NM_145169.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.21
• Publications: 0 publications found

Genes affected

SFT2D1 (HGNC:21102): (SFT2 domain containing 1) Predicted to be involved in protein transport and vesicle-mediated transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009871125).
• BP6: Variant 6-166324574-C-G is Benign according to our data. Variant chr6-166324574-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2351737.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145169.3. 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
	SFT2D1	NM_145169.3	MANE Select	c.373G>C	p.Val125Leu	missense	Exon 6 of 8	NP_660152.1	Q8WV19
	SFT2D1	NR_130112.2		n.460G>C		non_coding_transcript_exon	Exon 7 of 9
	SFT2D1	NR_130113.2		n.403-1688G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFT2D1	ENST00000361731.4	TSL:1 MANE Select	c.373G>C	p.Val125Leu	missense	Exon 6 of 8	ENSP00000354590.3	Q8WV19
	SFT2D1	ENST00000479490.1	TSL:1	n.115G>C		non_coding_transcript_exon	Exon 1 of 2
	SFT2D1	ENST00000487841.5	TSL:1	n.462G>C		non_coding_transcript_exon	Exon 7 of 8

Frequencies

GnomAD3 genomes AF: 0.000236 AC: 36 AN: 152242 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000252 AC: 63 AN: 250240 AF XY: 0.000332

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000884

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.000264

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000209 AC: 305 AN: 1460660 Hom.: 3 Cov.: 31 AF XY: 0.000238 AC XY: 173 AN XY: 726746

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.000227 AC: 10 AN: 44086

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39616

South Asian (SAS) AF: 0.000755 AC: 65 AN: 86040

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53406

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5768

European-Non Finnish (NFE) AF: 0.000163 AC: 181 AN: 1111816

Other (OTH) AF: 0.000514 AC: 31 AN: 60336

GnomAD4 genome AF: 0.000236 AC: 36 AN: 152360 Hom.: 0 Cov.: 33 AF XY: 0.000268 AC XY: 20 AN XY: 74512

African (AFR) AF: 0.0000240 AC: 1 AN: 41586

American (AMR) AF: 0.000392 AC: 6 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5192

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68034

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.000179 Hom.: 0

Bravo AF: 0.000268

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.000346 AC: 42

EpiCase AF: 0.000546

EpiControl AF: 0.000593

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	0.054
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.0030
DANN	Benign	0.14
DEOGEN2	Benign	0.0079	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.0099	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.1	N
PhyloP100		-1.2
PrimateAI	Benign	0.38	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.14
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.36
MutPred		0.49		Gain of helix (P = 0.0425)
MVP		0.14
MPC		0.15
ClinPred		0.0059	T
GERP RS		-10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.019
gMVP		0.50
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs201368298; hg19: chr6-166738062; COSMIC: COSV106107865; COSMIC: COSV106107865;