chr16-67228863-C-T

Variant names:

• chr16-67228863-C-T
• rs34502419
• NM_014187.4:c.366C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_014187.4(TMEM208):​c.366C>T​(p.Val122Val) variant causes a synonymous change. The variant allele was found at a frequency of 0.000967 in 1,614,020 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00071 (6 hom.)
• Consequence: TMEM208 NM_014187.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.41
• Publications: 2 publications found

Genes affected

TMEM208 (HGNC:25015): (transmembrane protein 208) This gene encodes a highly conserved protein which is localized in the endoplasmic reticulum (ER). The protein is linked to autophagy and ER stress. Knockdown of this gene increased autophagy and triggered ER stress. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 16-67228863-C-T is Benign according to our data. Variant chr16-67228863-C-T is described in ClinVar as Benign. ClinVar VariationId is 791557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014187.4. 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
	TMEM208	NM_014187.4	MANE Select	c.366C>T	p.Val122Val	synonymous	Exon 5 of 6	NP_054906.2	Q9BTX3-1
	TMEM208	NM_001318217.2		c.156C>T	p.Val52Val	synonymous	Exon 5 of 6	NP_001305146.1	J3KRY7
	TMEM208	NR_134524.2		n.481C>T		non_coding_transcript_exon	Exon 5 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM208	ENST00000304800.14	TSL:1 MANE Select	c.366C>T	p.Val122Val	synonymous	Exon 5 of 6	ENSP00000305892.9	Q9BTX3-1
	TMEM208	ENST00000565201.1	TSL:2	c.366C>T	p.Val122Val	synonymous	Exon 5 of 5	ENSP00000454579.1	H3BMW4
	TMEM208	ENST00000563953.5	TSL:2	c.156C>T	p.Val52Val	synonymous	Exon 5 of 6	ENSP00000462217.1	J3KRY7

Frequencies

GnomAD3 genomes AF: 0.00348 AC: 530 AN: 152222 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00130 AC: 323 AN: 249208 AF XY: 0.00107

Gnomad AFR exome AF: 0.0124

Gnomad AMR exome AF: 0.00197

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000398

Gnomad OTH exome AF: 0.00264

GnomAD4 exome AF: 0.000705 AC: 1031 AN: 1461680 Hom.: 6 Cov.: 32 AF XY: 0.000675 AC XY: 491 AN XY: 727134

African (AFR) AF: 0.0137 AC: 457 AN: 33476

American (AMR) AF: 0.00179 AC: 80 AN: 44722

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

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53398

Middle Eastern (MID) AF: 0.00607 AC: 35 AN: 5768

European-Non Finnish (NFE) AF: 0.000305 AC: 339 AN: 1111848

Other (OTH) AF: 0.00187 AC: 113 AN: 60374

GnomAD4 genome AF: 0.00347 AC: 529 AN: 152340 Hom.: 1 Cov.: 32 AF XY: 0.00346 AC XY: 258 AN XY: 74494

African (AFR) AF: 0.0112 AC: 467 AN: 41570

American (AMR) AF: 0.00183 AC: 28 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68034

Other (OTH) AF: 0.00379 AC: 8 AN: 2110

Alfa AF: 0.00211 Hom.: 2

Bravo AF: 0.00391

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	7.9
DANN	Benign	0.84
PhyloP100		4.4
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs34502419; hg19: chr16-67262766;